Combinatorial targeting of PI3K/AKT pathway with BKM120 increases cisplatin sensitivity and apoptotic response in...

Despite significant advancements in the treatment of non-small cell lung cancer (NSCLC) using conventional therapeutic methods, drug resistance remains a major factor contributing to disease recurrence. In this study, we aimed to explore the potential benefits of combining PI3K inhibition with Cisplatin in the context of NSCLC-derived A549 cells. Human non-small cell lung cancer A549 cells were cultured and treated with BKM120, cisplatin, or their combination. Cell viability was assessed using the MTT assay. Drug interactions were evaluated by calculating combination and dose reduction indices. Cell cycle progression and apoptosis were analyzed by flow cytometry. Quantitative real-time PCR was performed to measure the expression of key genes related to the cell cycle, apoptosis, autophagy, and proteasome function. The effects of autophagy and proteasome inhibition were further examined using chloroquine and bortezomib, respectively. Our findings demonstrated that BKM120 sensitized A549 cells to Cisplatin at lower concentrations. Moreover, we observed that BKM120 enhanced the anti-proliferative effects of Cisplatin by inducing cell cycle arrest in the G1 phase and upregulating the expression of P21 and FOXO4. Moreover, our real-time PCR analysis provided evidence that the combination treatment not only down-regulated Bcl-2 expression but also upregulated BAD and BAX expression in A549 cells, which ultimately led to apoptotic-mediated cell death. In conclusion, this investigation illuminated the role of PI3K inhibition in the chemo-sensitivity of 549 cells and revealed that the combination of BKM120 and Cisplatin may represent a viable therapeutic option for NSCLC.