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Volume 47
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10.3390/cimb47110902
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Article

Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model

by
Jae Heon Kim
1,†,
Miho Song
1,†,
Jeongkun Lee
2,
Sang Hun Lee
2,* and
Yun Seob Song
1,*
1
Department of Urology, Soonchunhyang University School of Medicine, Seoul 04401, Republic of Korea
2
Program in Biomedical Sciences, Department of Biomedical Sciences, College of Medicine, Engineering Inha University, Incheon 22212, Republic of Korea
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Curr. Issues Mol. Biol. 2025, 47(11), 902; https://doi.org/10.3390/cimb47110902
Submission received: 8 September 2025 / Revised: 15 October 2025 / Accepted: 18 October 2025 / Published: 30 October 2025
(This article belongs to the Topic Antibody-Mediated Therapy and Other Emerging Therapies in Cancer Treatment)
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Abstract

Castration-resistant prostate cancer (CRPC) remains difficult to treat with conventional chemotherapy. We evaluated a stem cell-based enzyme-prodrug strategy using hTERT-immortalized adipose-derived stem cells engineered to express rabbit carboxylesterase 2 (hTERT-ADSC.CE2) in combination with irinotecan (CPT-11). hTERT-ADSC.CE2 cells were generated via lentiviral transduction and confirmed to overexpress CE2. Their tumor-homing capacity toward PC3 prostate cancer cells was assessed, along with prodrug activation, apoptosis induction, and in vivo tumor suppression in a CRPC mouse model. hTERT-ADSC.CE2 cells demonstrated enhanced migration toward PC3 cells and higher expression of tumor-homing factors than the controls. Under CPT-11, they exhibited a strong “suicide” effect and induced selective killing of PC3 cells, with upregulation of BAX and cleaved caspase-3 and downregulation of BCL-2. By day 14, the combination arm showed significantly lower tumor burden than both the control and irinotecan-alone arms (p < 0.05). The pattern is consistent with intratumoral activation and localized SN-38 exposure. hTERT-ADSC.CE2 combined with irinotecan provides potent, tumor-targeted cytotoxicity and markedly suppresses CRPC progression. This cell-mediated prodrug activation system may represent a promising therapeutic approach for advanced prostate cancer.
Keywords: stem cells; prostate cancer; carboxylesterase stem cells; prostate cancer; carboxylesterase

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MDPI and ACS Style

Kim, J.H.; Song, M.; Lee, J.; Lee, S.H.; Song, Y.S. Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model. Curr. Issues Mol. Biol. 2025, 47, 902. https://doi.org/10.3390/cimb47110902

AMA Style

Kim JH, Song M, Lee J, Lee SH, Song YS. Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model. Current Issues in Molecular Biology. 2025; 47(11):902. https://doi.org/10.3390/cimb47110902

Chicago/Turabian Style

Kim, Jae Heon, Miho Song, Jeongkun Lee, Sang Hun Lee, and Yun Seob Song. 2025. "Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model" Current Issues in Molecular Biology 47, no. 11: 902. https://doi.org/10.3390/cimb47110902

APA Style

Kim, J. H., Song, M., Lee, J., Lee, S. H., & Song, Y. S. (2025). Combination Treatment of Carboxyl Esterase 2-Overexpressing hTERT-Immortalized Human Adipose Stem Cells Enhances the Inhibition of Tumor Growth by Irinotecan in PC3, a Castration-Resistant Prostate Cancer Model. Current Issues in Molecular Biology, 47(11), 902. https://doi.org/10.3390/cimb47110902

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