Synergistic effects of docetaxel and anti-PD-L1 therapy on prostate cancer cells: Modulation of apoptosis and PI3K/AKT/mTOR signaling pathway
Umar Saeed, Zahra Zahid PirachaABSTRACT
Background:
Prostate cancer (PCa) is a significant contributor to cancer-related morbidity and mortality worldwide. Advanced stages of PCa often develop resistance to standard chemotherapy and show limited response to immune checkpoint inhibitors, highlighting the urgent need for novel therapeutic strategies.
Objectives:
This study investigates the combined effects of docetaxel chemotherapy and anti-PD-L1 therapy on prostate cancer cells, focusing on enhancing apoptosis and targeting the PI3K/AKT/mTOR signaling pathway, a key driver of cancer progression and therapy resistance.
Materials and Methods:
PC-3 prostate cancer cells were treated with docetaxel, anti-PD-L1, or their combination. Cell viability was evaluated using MTT assays. Western blotting assessed apoptosis-related markers (BAX, cleaved caspase 3, cleaved PARP) and signaling proteins (PI3K/AKT/mTOR, p53, PTEN). Confocal microscopy was employed to analyze BAX nuclear translocation.
Results:
Combination therapy markedly decreased cell viability compared to single treatments. Apoptosis was significantly enhanced, with increased expression of BAX, cleaved caspase 3, and cleaved PARP. The therapy effectively inhibited the PI3K/AKT/mTOR pathway and restored tumor suppressors p53 and PTEN. Nuclear translocation of BAX, confirmed via confocal microscopy, underscored apoptosis induction.
Conclusion:
Docetaxel and anti-PD-L1 combination therapy synergistically enhances apoptosis and disrupts key resistance mechanisms in PCa, offering a promising avenue for advanced prostate cancer treatment.