Investigation of the in vitro synergistic anticancer effects of the BCL-2 inhibitor navitoclax and the HSP27 inhibitor J2 on lung adenocarcinoma

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common subtypes of lung cancer and represents an aggressive and clinically significant malignancy characterized by treatment resistance and the suppression of apoptotic mechanisms. In this study, the A549 cell line was used as a model system to investigate the in vitro synergistic anticancer effects of the Bcl-2 inhibitor Navitoclax and the HSP27 inhibitor J2 in NSCLC. Cell viability was assessed using the MTT assay, drug interactions were evaluated using CompuSyn and the Bliss independence model, and dose–response relationships were analyzed through response surface methodology (RSM). In addition, the expression levels of the BCL2, BAX, APAF-1, CTNNB1, and CASP9 genes were determined by RT-qPCR, while Bax, Bcl-2, and Caspase-3 protein levels were analyzed using ELISA. According to the Bliss analysis, the most pronounced synergistic effect in the inversely proportional combination was observed at 0.625 µM Navitoclax + 10 µM J2, whereas in the directly proportional combination, it was detected at 0.625 µM Navitoclax + 0.156 µM J2. These findings suggest that the combination may exert a more selective antiproliferative effect on A549 cells.