AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025160127
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ORIGINAL RESEARCH ARTICLE

Regulation of X-linked inhibitor of apoptosis protein by androgen deprivation therapy promotes castration-resistant prostate cancer progression

Ke Ren1* ,  Xin Gou1 ,  Weiyang He1
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1 Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
EJMO, 025160127 https://doi.org/10.36922/EJMO025160127
Received: 17 April 2025 | Revised: 21 June 2025 | Accepted: 1 July 2025 | Published online: 5 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Hormone-sensitive prostate cancer typically progresses to a castration-resistant stage after an average of 18–24 months of androgen deprivation therapy (ADT). The anti-apoptotic factor X-linked inhibitor of apoptosis protein (XIAP) is not only implicated in the development of prostate cancer but also plays a critical role in its progression to the castration-resistant state.

Objective: This study aims to investigate the relationship between ADT and the regulation of XIAP.

Methods: The protein expression levels of midline 1 (MID1), serine/threonine kinase proviral integration site for Moloney murine leukemia virus 2 (PIM2), protein phosphatase 2A (PP2A), eukaryotic translation initiation factor 4B (EIF4B), phosphorylated EIF4B, and XIAP were analyzed and compared among castration-naïve, hormone-sensitive, and castration-resistant prostate cancer (CRPC) tissues. The MID1 gene was manipulated in both androgen-dependent and androgen-independent prostate cancer cells to evaluate its effect on XIAP protein expression and the apoptosis rate of the prostate cancer cells.

Results: XIAP protein expression and EIF4B phosphorylation levels were significantly increased in CRPC. In contrast, PIM2 and EIF4B protein expression levels remained similar before and after the development of castration resistance. MID1 protein expression level was significantly elevated, while PP2A expression was significantly reduced in CRPC tissues.

Conclusion: ADT may lead to elevated MID1 and reduced PP2A protein expression levels, which indirectly enhance the phosphorylation activity of PIM2 on EIF4B, thereby increasing XIAP expression and reducing apoptosis in prostate cancer cells. This mechanism likely contributes to disease progression toward the castration-resistant stage.

Keywords
Androgen deprivation therapy
Apoptosis
Castration-resistant prostate cancer
X-linked inhibitor of apoptosis protein
Funding
This research was supported by the Natural Science Foundation of Chongqing (cstc2021jcyj-msxmX0122; cstc2016jcjA0099) and the Natural Science Foundation of China (No. 81101945).
Conflict of interest
The authors declare that they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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