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

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.