AccScience Publishing / ARNM / Online First / DOI: 10.36922/ARNM025160018
ORIGINAL RESEARCH ARTICLE

Role of phosphatidylinositol-3-kinase/protein kinase B signaling in androgen-independent prostate cancer progression

Fengmei Cai1 Ying Zhao1 Lili Yang1 Jia Wang1 Wei Qian1 Ge Zhang1 Hongmei Qiao2* Huilian Hou3*
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1 Department of Pathology, Xi’an Fourth Hospital, Xi’an, Shaanxi, China
2 Department of Oncology, Gansu Wuwei Cancer Hospital, Wuwei, Gansu, China
3 Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
Received: 18 April 2025 | Revised: 17 June 2025 | Accepted: 4 July 2025 | Published online: 29 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Prostate cancer (PCa) is a leading cause of cancer-related deaths in males. Over time, many patients develop castration-resistant PCa, which is associated with a poor prognosis. Although the mechanisms underlying treatment failure remain unclear, the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway plays an important role in the failure of castration treatment. This study aims to explore the role of the PI3K/Akt pathway in androgen-independent PCa (AIPC) using clinical data and validate the cellular-level experimental findings by analyzing the expression of androgen receptor (AR), PI3K, and Akt in PCa. Patients were classified into two groups: AIPC (n = 38) and androgen-dependent PCa (ADPC) (n = 38). The expression levels of AR, PI3K, or Akt were evaluated through immunohistochemical analysis. Statistical analyses were performed to examine the correlations among AR, PI3K, and Akt. Significant differences (p < 0.01) were observed between groups with prostate-specific antigen levels ≤20 ng/mL and >20 ng/mL. The Gleason score in the AIPC group was significantly higher than in the ADPC group (p < 0.01). Positive expression of AR, PI3K, and phosphorylated Akt was observed in the nucleus, cytoplasm, and both the cytoplasm and nucleus, respectively. In AIPC patients, AR, PI3K, and Akt were positively correlated, confirming the clinical relevance of PI3K and Akt in the progression of AIPC. These findings suggest that the PI3K/Akt pathway serves as a potential regulator of AR activation and plays a crucial role in the progression of AIPC.

Keywords
Androgen receptor
Phosphatidylinositol-3-kinase
Protein kinase B
Androgen-independent prostate cancer
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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Advances in Radiotherapy & Nuclear Medicine, Electronic ISSN: 2972-4392 Print ISSN: 3060-8554, Published by AccScience Publishing