Next Article in Journal
CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study
Next Article in Special Issue
Erdafitinib Resensitizes ABCB1-Overexpressing Multidrug-Resistant Cancer Cells to Cytotoxic Anticancer Drugs
Previous Article in Journal
Metabolic Parameters Influence Brain Infarction and Outcome after Resection of Brain Metastases
Previous Article in Special Issue
Nelfinavir Inhibits the TCF11/Nrf1-Mediated Proteasome Recovery Pathway in Multiple Myeloma
Open AccessArticle

Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B More Efficiently Than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptors

1
Department of Bioengineering, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
2
Faculty of Biology, M.V. Lomonosov Moscow State University, 119992 Moscow, Russia
3
Department of Immunology, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia
4
Department of X-ray and Synchrotron Research, A.V. Shubnikov Institute of Crystallography of Federal Scientific Research Centre “Crystallography and Photonics” of Russian Academy of Sciences, 119333 Moscow, Russia
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(5), 1129; https://doi.org/10.3390/cancers12051129
Received: 18 March 2020 / Revised: 24 April 2020 / Accepted: 28 April 2020 / Published: 30 April 2020
(This article belongs to the Collection Drug Resistance and Novel Therapies in Cancers)
TRAIL is considered a promising antitumor agent because it causes apoptosis of transformed cells without affecting normal cells. However, many types of tumors are cytokine resistant, and combination therapy with various chemotherapeutic drugs is being developed to overcome the resistance. We have demonstrated that the combination of TRAIL with doxorubicin, bortezomib, and panobinostat dramatically reduced the viability of TRAIL-resistant A549 and HT-29 cells. Chemotherapy even more efficiently sensitized cells to the DR5-specific mutant variant of TRAIL DR5-B, which does not have an affinity for decoy receptors. Bortezomib and doxorubicin greatly enhanced the surface expression of the death receptors DR5 and DR4, while panobinostat increased expression of DR5 and suppressed expression of DR4 in both cell lines. All drugs increased surface expression of the decoy receptors DcR1 and DcR2. Unlike the combined treatment, if the cells were pretreated with chemotherapy for 24 h, the cytotoxic activity of TRAIL was less pronounced, while sequential treatment of cells enhanced the effectiveness of DR5-B. The same results were obtained with agonistic anti-DR5 antibodies. Thus, the effectiveness of TRAIL was rather limited due to changes in the ratio of death and decoy receptors and DR5-specific agonists may be preferred in combination antitumor therapy regimens. View Full-Text
Keywords: TRAIL; DR5-B; DR4; DR5; DcR1; DcR2; doxorubicin; bortezomib; panobinostat TRAIL; DR5-B; DR4; DR5; DcR1; DcR2; doxorubicin; bortezomib; panobinostat
Show Figures

Figure 1

MDPI and ACS Style

Artykov, A.A.; Belov, D.A.; Shipunova, V.O.; Trushina, D.B.; Deyev, S.M.; Dolgikh, D.A.; Kirpichnikov, M.P.; Gasparian, M.E. Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B More Efficiently Than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptors. Cancers 2020, 12, 1129. https://doi.org/10.3390/cancers12051129

AMA Style

Artykov AA, Belov DA, Shipunova VO, Trushina DB, Deyev SM, Dolgikh DA, Kirpichnikov MP, Gasparian ME. Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B More Efficiently Than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptors. Cancers. 2020; 12(5):1129. https://doi.org/10.3390/cancers12051129

Chicago/Turabian Style

Artykov, Artem A.; Belov, Dmitry A.; Shipunova, Victoria O.; Trushina, Daria B.; Deyev, Sergey M.; Dolgikh, Dmitry A.; Kirpichnikov, Mikhail P.; Gasparian, Marine E. 2020. "Chemotherapeutic Agents Sensitize Resistant Cancer Cells to the DR5-Specific Variant DR5-B More Efficiently Than to TRAIL by Modulating the Surface Expression of Death and Decoy Receptors" Cancers 12, no. 5: 1129. https://doi.org/10.3390/cancers12051129

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop