Search Results (16,580)

Background/Objectives: The clinical challenges of PARP inhibitors in ovarian cancer include the lack of effective maintenance regimens for homologous recombination proficiency (HRP) patients and the emergence of acquired resistance in initially responsive homologous recombination deficiency (HRD) patients. This study aims to explore the synergistic effect and molecular mechanism of the bispecific tyrosine phosphorylation-regulated kinase 1B (DYRK1B) inhibitor AZ191 combined with the PARP inhibitor Niraparib on high-grade serous ovarian cancer (HGSOC). Methods: This study first explored the expression and prognostic significance of DYRK1B in ovarian cancer through bioinformatics analysis. Subsequently, the therapeutic effect of the DYRK1B inhibitor AZ191 combined with Niraparib on HGSOC cells and organoids was evaluated by MTT examination. Flow cytometry and Western blot were used to investigate the synergistic mechanism between the two agents. Results: Bioinformatics analysis shows that the high expression of DYRK1B in serous ovarian cancer is associated with poor prognosis of the patients. The experiments in vitro have shown that the DYRK1B inhibitor AZ191 can enhance the therapeutic effect of Niraparib on HGSOC cells and organoids, whether HRD-positive or not. Mechanistic studies have shown that the combination of AZ191 and Niraparib can synergistically increase the accumulation of DNA damage, thereby intensifying the apoptosis of HGSOC cells. In addition, the combination therapy induces ferroptosis by inhibiting the Nrf2/SLC7A11/GPX4 axis, thereby exerting cytotoxic effects. Conclusions: Our results uncover a novel mechanism by which inhibiting DYRK1B enhances the anti-HGSOC efficacy of Niraparib and may offer a promising treatment strategy to improve the maintenance therapy in both HRD and HRP ovarian cancer patients. Full article

Background: Electrochemotherapy enhances the intracellular delivery of anticancer agents through electroporation but is traditionally limited to cytotoxic drugs associated with significant side effects. Vitamin C (ascorbic acid) exhibits selective anticancer activity when accumulated at high intracellular concentrations; however, its therapeutic application is restricted by poor membrane permeability and rapid systemic clearance. Methods: In this study, we investigated whether reversible electroporation, applied using a custom-designed variable plate electrode system designed to deliver a uniform electric field, could potentiate the antitumor efficacy of low-dose vitamin C. Numerical simulations were performed to optimize electrode spacing and stimulation voltage, suggesting homogeneous electric field coverage throughout the tumor volume. The proposed approach was evaluated in vitro using MDA-MB-231 and 4T1 breast cancer cell lines and in vivo in a 4T1 murine breast cancer model. Results: Low-dose vitamin C alone produced minimal cytotoxic effects, whereas its combination with electroporation significantly reduced cell viability and increased apoptotic and necrotic cell death in vitro. In vivo, vitamin C–assisted electrochemotherapy resulted in pronounced tumor growth suppression, with tumor volumes reduced to approximately 0.34-fold of baseline by day 15, accompanied by decreased proliferation and marked tissue disruption. Conclusions: These findings demonstrate that uniform-field reversible electroporation markedly enhances the intracellular delivery and antitumor activity of low-dose vitamin C, supporting this technology-driven strategy as a promising, low-toxicity alternative to conventional chemotherapeutic agents in electrochemotherapy for solid tumors. Full article

This study reports the effect of polyethyleneimine’s molecular weight (PEI, Mn: 1200, 10,000, and 60,000 g/mol, denoted as PEI_1.2, PEI₁₀, and PEI₆₀) on the physical, chemical, and biological characteristics of carbon dots (Cdots) derived from chitosan (Chi) and PEI (Chi-PEI Cdots). The size of Chi Cdots was 41.5 ± 6.1 nm, which increased to 50.9 ± 5.9, 71.4 ± 4.2, and 93.3 ± 7.4 nm with the preparation of Chi-PEI_1.2, Chi-PEI₁₀ and Chi-PEI₆₀ Cdots. The fluorescence properties and quantum yield% values of the Cdots prepared from Chi, PEI_1.2, PEI₁₀, and PEI₆₀ and their corresponding biopolymeric Chi-PEI Cdots were compared. A higher quantum yield of 26 ± 1.6% was observed for Chi-PEI_1.2. This decreased with the increasing molecular weight of PEI and was calculated to be 15 ± 1.9% for Chi-PEI₆₀. All the prepared bare Chi, bare PEI and corresponding bipolymeric Chi-PEI Cdots were observed to be nonhemolytic up to a 1 mg/mL concentration. Lower cytotoxic properties were observed for Chi-PEI Cdots on L929 fibroblast cells compared to their corresponding bare forms. Higher cell viability was observed for Chi-PEI_1.2 Cdots with 95% viability in the presence of a 1000 µg/mL concentration. The antibacterial activity of the prepared Cdots against pathogens such as E. coli, K. pneumoniae, S. aureus, B. subtilis, and C. albicans was investigated and compared. Lower MIC and MBC values were determined for Chi-PEI₁₀ against C. albicans with values of 12.5 and 50 mg/mL, respectively. Although the antibacterial properties of Chi-PEI Cdots were less strong than those of bare Cdots derived from individual Chi and PEI molecules, their light-induced antibacterial activities were found to be better. Full article

Natural bioactive polysaccharides have been investigated for their ability to modulate antiviral immune responses. Polysaccharide peptide (PSP) from Coriolus versicolor previously restricted human immunodeficiency virus type 1 (HIV-1) entry into monocytic cells through a protein kinase R (PKR)-dependent cytoskeletal mechanism. However, its impact on antiviral signaling in adaptive cluster of differentiation 4 (CD4)+ T-cell models remains incompletely defined. Here, we evaluated concentration- and time-dependent effects of PSP (50–1000 µg/mL) in Jurkat T cells over 3 and 6 days. Cell viability was assessed by MTT, trypan blue exclusion, and viable cell density analysis. Immunoblotting and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to examine Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), signal transducer and activator of transcription 1 and 2 (STAT1/STAT2), PKR, interferon gamma (IFN-γ), and cofilin-1 signaling. PSP did not induce cytotoxicity at any concentration. Instead, PSP promoted dose- and time-dependent upregulation of intracellular TLR4, PKR, phospho-PKR (Thr446), Cofilin-1, phospho-Cofilin-1 (Ser3), phospho-STAT1 (Tyr701), phospho-STAT2 (Tyr690), phospho-NF-κB (Ser536), and IFN-γ, with amplified responses at Day 6. These changes were paralleled by transcriptional induction of antiviral-associated genes. Collectively, PSP induces coordinated interferon (IFN)-associated and cytoskeletal regulatory signaling in Jurkat T cells without cytotoxicity, providing a mechanistic framework for future evaluation of viral permissiveness and antiviral responses in adaptive immune models. Full article

Acute myeloid leukemia (AML) remains a highly morbid malignancy in which outcomes are constrained not only by disease refractoriness and relapse, but also by therapy-related toxicity—particularly infections, mucosal injury, and delayed hematopoietic reconstitution. The gut microbiota has emerged as a potentially modifiable layer of host vulnerability and resilience during AML treatment. Microbiome disruption is detectable already at diagnosis, even in antibiotic-naïve patients, and is often characterized by reduced community diversity, depletion of anaerobic taxa linked to short-chain fatty acids (SCFAs) production, and enrichment of pathobiont-associated profiles. During induction, cytotoxic therapy and antimicrobials precipitates diversity loss, domination events, and persistent shifts beyond discharge. Clinically, the most consistent translational signal is the association between baseline or early-treatment microbiome features and infectious outcomes, while emerging data suggest that diagnosis-time microbiome structure may also relate to hematologic recovery kinetics. Mechanistic models converge on pathways linking barrier integrity, microbial metabolites (notably butyrate and other SCFAs), immune calibration, and inflammatory translocation of microbial products. These insights support hypotheses: antimicrobial stewardship may preserve microbiome function; ecosystem repair strategies such as autologous fecal microbiota transfer (A-FMT) are feasible and can restore community structure; and metabolite or nutritional interventions merit evaluation in immunocompromised hosts. Regimen-specific microbiome effects and microbiome–drug interactions suggest that treatment choice could have downstream microbiome-mediated consequences. We synthesize evidence, outline interventional concepts, and define methodological priorities for next-generation trials assessing causality and clinical benefit. Progress will require longitudinal sampling, multi-omic integration (metabolomics, resistomics, and barrier/inflammatory biomarkers), and interventional designs linking microbiome dynamics to clinically meaningful outcomes. Full article

Telmisartan, an angiotensin II type 1 receptor blocker with established anti-inflammatory and antihypertensive properties, has been reported to inhibit tumor cell proliferation, yet its impact on the tumor immune microenvironment remains poorly understood. In this study, we evaluated the immunomodulatory effects of telmisartan using a syngeneic MC38 colorectal cancer model in C57BL/6 mice. Daily intragastric administration of telmisartan significantly suppressed tumor growth and reduced endpoint tumor weight compared with controls. To elucidate the underlying mechanisms, we performed single-cell RNA sequencing on tumor-infiltrating CD45⁺ immune cells and revealed a macrophage-dominated immune landscape comprising multiple transcriptionally distinct subclusters. Telmisartan broadly downregulated pro-tumoral and M2-associated macrophage programs, including decreased expression of genes such as Mrc1 and Spp1, while also suppressing cell proliferation-related pathways. In contrast to its overall suppressive impact on macrophages, telmisartan increased the proportion of cytotoxic CD8⁺ T cells, reduced regulatory T cell counts, and enhanced major histocompatibility complex class I antigen presentation, consistent with an immune-activating effect. These results indicate that telmisartan reshapes the colorectal tumor immune microenvironment by simultaneously attenuating tumor-promoting macrophage activity and augmenting cytotoxic T cell responses. Overall, this study provides a single-cell framework to understand how angiotensin receptor blockade reshapes tumor-infiltrating immune programs, highlighting the translational potential of repurposing telmisartan for novel cancer immunotherapy strategies. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Our previous study demonstrated that combination therapy with local hyperthermia (HT) and anti-CTLA-4 antibody (C4), an immune checkpoint inhibitor, induced regression of both local and distant tumors. However, tumor microenvironment (TME) changes in local and distant tumors following local HT and C4 remain unclear. Here, we aimed to evaluate TME changes in local and distant tumors induced by local HT + C4 therapy. Methods: Murine TNBC cells were inoculated in both legs of male BALB/cAJcl mice, and only one leg was treated with HT (42.5 °C for 20 min). C4 was administered intraperitoneally every 3 days for a total of three doses. For CD4⁺ T cell depletion experiments, anti-CD4 antibody (αCD4) was administered intraperitoneally every 3 days for a total of 12 doses. Tumor-infiltrating immune cells in locally heated tumors and unheated distant tumors were analyzed 9 days after the initial treatment. Furthermore, tumor growth in heated tumors and unheated distant tumors under αCD4 administration was evaluated. Results: HT + C4 therapy increased the proportion of helper T cells and elevated the ratio of cytotoxic T cells plus helper T cells to myeloid-derived suppressor cells in both heated tumors and unheated distant tumors. The HT + C4 + αCD4 group exhibited significantly larger tumor growth, compared with the HT + C4 group in both HT (p < 0.01) and unheated distant tumors (p < 0.01). Conclusions: These results suggest that combination therapy of HT and C4 favorably modulates the TME. CD4⁺ T cell infiltration may contribute to both local and distant antitumor effects. Full article

Macrophages are highly plastic cells of the tumor microenvironment, and although classically activated M1 macrophages are generally regarded as anti-tumor effectors, their prolonged cytotoxic activity may also promote tumor adaptation. In this study, we investigated whether sustained exposure of prostate cancer cells to cytotoxic M1-like macrophages results in the selection of tumor cell populations with enhanced malignant properties. Macrophage-resistant derivatives of the human prostate cancer cell lines PC3 and DU145 were generated by repeated co-culture with cytotoxic THP-1-derived macrophages and characterized in vitro and in vivo. Macrophage-selected tumor cells showed increased proliferative activity and enhanced clonogenic survival. In vivo, these cells formed larger xenograft tumors with more aggressive histopathological features. At the same time, their migratory activity was not significantly increased, although they displayed partial epithelial–mesenchymal transition-like changes, including increased vimentin expression without a marked loss of epithelial markers. Transcriptomic profiling revealed coordinated inflammatory and adaptive reprogramming, characterized by the enrichment of cytokine- and immune-response pathways together with the suppression of metabolic and differentiation-associated programs. These changes were accompanied by the selective activation of p38 MAPK signaling, while sensitivity to paclitaxel remained unchanged. Taken together, the results indicate that macrophage cytotoxicity may act as a selective pressure promoting the emergence of inflammation-adapted tumor cell variants with increased malignant potential, supporting re-evaluation of the role of M1-like macrophages in tumor progression. Full article

Tranilast, an anti-allergic drug with well-established anti-inflammatory, antifibrotic, and antiproliferative properties, suffers from poor water solubility and low bioavailability, which limit its therapeutic potential. To improve its pharmacological profile, we designed and synthesized a novel series of hydroxylated Tranilast analogues. The compounds were obtained through a green, single-step coupling reaction between activated methoxy-substituted hydroxycinnamic acids and anthranilic or hydroxyanthranilic acids, using a triethylamine–isobutyl chloroformate system in environmentally friendly solvents. Fifteen derivatives were isolated in good to excellent yields (63–94%) without chromatographic purification. The synthesized compounds were evaluated for antimicrobial, antioxidant, anti-inflammatory, and antiproliferative activities. Several analogues displayed notable antimicrobial effects against Candida albicans, Staphylococcus aureus, and Klebsiella pneumoniae, with minimum inhibitory concentrations as low as 75 µg/mL. Hydroxylated derivatives showed enhanced radical-scavenging activity in DPPH and ABTS assays compared with Tranilast. Selected compounds also demonstrated suggestive antiproliferative effects against LNCaP prostate cancer cells while maintaining low cytotoxicity toward HaCaT keratinocytes, indicating favourable selectivity. Furthermore, some derivatives significantly reduced nitric oxide production in LPS-stimulated HaCaT cells, confirming their anti-inflammatory potential. Overall, hydroxylation proves to be an effective strategy for improving the biological profile of Tranilast, yielding promising candidates for further pharmacological development. Full article

Modification of PLA with functional nanoparticles is a promising approach for imparting new properties to the material. In this work, titanium nanoparticles (Ti NPs) and titanium dioxide nanoparticles (TiO₂ NPs) were synthesized by laser ablation and characterized by dynamic light scattering, spectrophotometry, and transmission electron microscopy. The average hydrodynamic diameter of Ti NPs was 12 nm, while that of TiO₂ NPs was 24 nm; both dispersions possessed a positive zeta potential (23–27 mV) and spherical morphology. L-PLA composite films containing 0.1 wt.% Ti NPs or TiO₂ NPs were obtained by solution casting. Atomic force and modulation-interference microscopy confirmed the uniform distribution of nanoparticles within the polymer matrix, although partial aggregation was observed. The introduction of TiO₂ NPs increased the water contact angle. Mechanical testing revealed a significant reinforcing effect: the addition of 0.1 wt.% NPs increased the Young’s modulus by 62–68% and the ultimate tensile strength by 16–18% while maintaining a ductile fracture pattern with elongation at break up to ~8%. Both types of composites generated reactive oxygen species (ROS) in aqueous solutions: Ti NPs increased H₂O₂ production by 5.5 times and TiO₂ NPs by 4.9 times, and they also induced the formation of hydroxyl radicals. The accumulation of 8-oxoguanine in DNA and long-lived oxidized protein species confirmed the materials’ ability to cause oxidative damage to biomacromolecules. For E. coli, growth inhibition reached 40.5% (for composites with Ti NPs) and 71% (for composites with TiO₂ NPs). The effect was even more pronounced for S. aureus, where inhibition levels were approximately 70% and 80%, respectively; flow cytometry confirmed the strong bactericidal effect, showing that materials containing TiO₂ NPs increased the proportion of dead cells to 25% for E. coli and ~68% for S. aureus. Cytotoxicity assessment on human fibroblasts (HSF) demonstrated the high biocompatibility of neat L-PLA and composites with Ti NPs (viability > 95%) and with TiO₂ NPs (viability ~93%). The obtained results indicate that L-PLA-based composites with Ti NPs and TiO₂ NPs exhibit pronounced ROS-mediated antibacterial activity without additional UV irradiation. These findings position these materials as highly promising candidates for active biodegradable food packaging to extend shelf-life and for biomedical devices, such as wound dressings and implants, where reducing the risk of bacterial colonization is critical. Full article

Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target antibacterial activity and its capacity to potentiate the effects of ciprofloxacin (CIP). Methods: The antibacterial and antivirulence properties of SIL were assessed using both in vitro and in silico approaches. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and its synergistic interaction with CIP was evaluated using checkerboard assays. Inhibition of biofilm formation, as well as disruption of established biofilms, was assessed using an MTT-based viability assay. Staphyloxanthin (STX) inhibition was examined through pigment extraction and spectrophotometric quantification of pathway intermediates. Molecular docking studies were conducted to predict the binding affinities of the compounds to key bacterial targets, while safety was evaluated through haemolytic and cytotoxicity assays. Results: SIL exhibited weak to moderate direct antibacterial activity (MICs of 256–512 µg/mL), which is characteristic of many natural product scaffolds. Notably, SIL potentiated the activity of CIP, reducing its MIC by up to fourfold against selected resistant strains of S. aureus. SIL significantly inhibited biofilm formation and disrupted established mature biofilms in a strain-dependent manner. In vitro metabolic profiling and in silico analyses provided mechanistic insights into the effects of SIL on STX biosynthesis. Precursor accumulation data suggest inhibition at the diapophytoene desaturase (CrtN) catalytic step, representing a potential mechanism not previously reported for flavonolignans. Molecular docking studies further predicted favourable binding affinities for CrtM and other key targets. Importantly, SIL exhibited no haemolytic activity and low cytotoxicity in macrophages at synergistic concentrations. Conclusions: This study provides evidence that SIL functions as a dual-action agent, potentiating ciprofloxacin efficacy while reducing STX production and inhibiting biofilm formation, thereby impairing key virulence mechanisms of S. aureus. These findings, together with its favourable safety profile, provide a strong rationale for the development of silibinin-based topical adjuvants to combat drug-resistant Staphylococcus infections in humans. Full article

Background/Objectives: To address the limitations of natural curcumin, this study focuses on the functional evaluation of structurally optimized derivatives. We aimed to elucidate structure–activity relationships (SAR) and the stage-specific molecular mechanisms of adipogenesis inhibition using an in vitro cellular assay. Methods: Four novel curcuminoids were synthesized and evaluated in 3T3-L1 preadipocytes against natural curcumin (Curcuminoid I). Efficacy and mechanisms were assessed via cell viability assays, quantitative Oil Red O staining, and time-dependent transcriptional profiling (qPCR/Western blotting) of the KLF family and master regulators. Results: SAR analysis identified Curcuminoid III (symmetric 3,5-dimethoxy-4-hydroxy) as the most potent and safe candidate, whereas Curcuminoid IV exhibited cytotoxicity. Time-course analysis revealed a distinct step-wise inhibition mechanism wherein Curcuminoid III significantly upregulated the differentiation repressor KLF2 at the immediate-early phase. This rapid modulation effectively prevented the subsequent induction of pro-adipogenic factors, including KLF9, KLF15, PPARγ, and C/EBPα, in the mid-stage (3–5 d). Consequently, the expression of the maturation marker aP2 was robustly suppressed by the late stage (5–7 d). Conclusions: The symmetric 3,5-dimethoxy-4-hydroxy substitution pattern appears to confer strong anti-adipogenic activity to Curcuminoid III. Early modulation of the KLF2–PPARγ axis at the onset of differentiation may initiate a cascading inhibitory effect throughout the adipogenic program. These findings highlight the potential of structurally optimized plant-derived bioactive compounds as regulators of metabolic cell fate. Full article

Tricholoma terreum, a mushroom rich in bioactive compounds, exhibits notable antioxidant and anticancer properties. Despite its traditional use, its effects on breast cancer metabolism remain underexplored. Here, we conducted comprehensive phytochemical and volatile organic compound profiling of T. terreum extracts and evaluated their cytotoxicity against MCF-7 breast cancer cells. Using SPME–GC–MS and HPLC, we identified a complex chemical matrix dominated by organic acids (acetic acid, 43.85%) and nitrogen-containing heterocyclics (2-acetylpyridine, 15.19%), alongside significant phenolic acids such as gallic acid and syringic acid. Biological assays indicated that the ethanol extract showed notable cytotoxic effects, reducing MCF-7 cell viability to 3.64% after 72 h, while higher viability was preserved in healthy CCD-1072sk fibroblast cells. Using cell viability assays, flow cytometry, and gene expression analysis, we found that ethanol extracts selectively reduced cancer cell viability, induced G0/G1 cell cycle arrest (71.92%), and promoted apoptosis. Mechanistically, treatment downregulated key nucleotide biosynthesis genes (DHFR, TK1) and the glycolytic enzyme gene (ENO1), while upregulating the oxidative stress response gene SLC7A11 (18.32-fold), suggesting disruption of cancer metabolic pathways. These findings reveal a metabolic reprogramming effect of T. terreum extracts, highlighting their potential as metabolism-targeted agents in breast cancer therapy. Further studies are warranted to validate these effects in vivo and isolate active constituents. Full article

Background/Objectives: Atopic dermatitis (AD)-related skin inflammation involves the release of cytokines and chemokines from keratinocytes; therefore, keratinocyte-based models are widely used to evaluate the anti-inflammatory potential of botanical extracts. This study examined the relationship between phytochemical profiles and anti-inflammatory potential of baobab fruit 30% and 70% ethanol extracts (BE-30 and BE-70, respectively) in a TNF-α/IFN-γ (TI)-stimulated HaCaT keratinocyte model. Methods: The anti-inflammatory effects of both extracts were evaluated by measuring cytokine and chemokine secretion in TI-stimulated HaCaT cells. Phytochemical characterization was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and targeted high-performance liquid chromatography (HPLC). Results: Both extracts were non-cytotoxic. TI-stimulation markedly increased interleukin (IL)-6, IL-8 and monocyte chemotactic protein (MCP)-1 secretion, while BE-30 and BE-70 significantly reduced all three mediators in a dose-dependent manner. At comparable doses, BE-70 exhibited greater inhibition than BE-30. BE-30 showed a non-monotonic IL-8 response at low concentrations, whereas BE-70 consistently reduced IL-8 in a dose-dependent manner. LC–MS/MS profiling revealed a polyphenol-rich composition, including flavonol glycosides and related phenolic compounds. HPLC confirmed the presence of four marker analytes (procyanidin B2, epicatechin, rutin and tiliroside), which were enriched in BE-70. The content of these four polyphenols was 1.94-fold higher in BE-70. Conclusions: Baobab fruit extracts exhibit anti-inflammatory activity associated with polyphenols. These findings suggest that they could be used as analytical standards and in dermatological applications. Full article

Natural killer (NK) cells are effector cells of the innate immune system. The cytokine microenvironment influences NK cell function. Dysregulation of NK cell cytotoxicity can manifest in reproductive disorders and is also observed in tumor-transformed tissues. The search for immunotherapies capable of regulating NK cell activity is therefore relevant. This study aimed to evaluate the effect of the TGFβ signaling pathway inhibitor and the cyclin-dependent kinase (CDK) 7/12/13 inhibitor on the transcriptional profile of NK-92 cell line. In the study, the cytokines TGFβ1, IL-12, IL-15, IL-18, and TNFα, and the TGFβ receptor type 1 (TGFβR1) inhibitor LY3200882 and the CDK7/12/13 inhibitor THZ1 were used. The cells were cultured sequentially in the presence of inhibitors and cytokines, followed by assessment of the gene expression of NCR2, NCR3, AHR, NCAM1, B3GAT1, EOMES, GATA3, KLRC1, KLRC2, CCL5, IL10 and TBX21. We observed direct effects of the inhibitors on NK cells. LY3200882 increased the expression of KLRC1 and B3GAT1, and reduced NCAM1. THZ1 increased the expression of KLRC1, KLRC2, AHR and EOMES, while it reduced IL-10 and NCR2. IL-12, IL-15, IL-18, and TNFα modified the gene expression of some phenotypic and cytotoxic receptors and transcription factors. TGFβ1 increased the expression of KLRC1, NCAM1, and B3GAT1. Blocking TGFβ-dependent signaling with LY3200882 abolished TGFβ1 effects. We assessed CD56 presence on NK-92 cell membrane and found its increase in the presence of LY3200882. After LY3200882 treatment, in the presence of TGFβ1 and choriocarcinoma cell line JEG-3, the expression of CD56 receptor on NK cell membrane decreased. Pretreating NK cells with THZ1 decreased the expression of NCAM1, B3GAT1, and EOMES in the presence of TGFβ1. Thus, LY3200882 partially neutralized TGFβ1 effects on the expression of NK cell receptor genes. THZ1 followed by TGFβ1 treatment promoted NK cell transcriptional profile characteristic for CD56dim NK cells. Both LY3200882 and THZ1 affected the NK cell transcription even without cytokine treatment. The independent effects of synthetic inhibitors on NK cells, as well as their influence in the presence of tumor cells, should be considered. Full article