Melissa officinalis Extract Reduces the Antiproliferative Efficacy of Osimertinib in NSCLC Cells by Inhibiting Apoptotic Signaling

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. The most significant problem in treatment is the resistance that develops over time against osimertinib (OSI), an irreversible, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits EGFR T790M resistance mutations, which are among the activating mutations of the EGFR. Many studies have shown that certain phytochemicals can overcome drug resistance in cancer cells. Additionally, the fact that they have fewer side effects compared to drugs has made plants popular in cancer treatment. Melissa officinalis (M. officinalis) is a plant with antiproliferative properties widely used in the treatment of various cancer types, having shown significant results in many human cancer cell lines. In this study, the antagonistic anticancer effect of M. officinalis plant extract and osimertinib was investigated on the PC-9 NSCLC cell line. According to the calculation of the results obtained by the MTT method using CompuSyn software, the combination of 50 nM osimertinib and 50 µg ml-1 M. officinalis methanol extract showed the best antagonistic effect (CI: 3031.44) after 48h of incubation in PC-9 cells. The gene expression levels and protein levels of BCL-2 associated X protein (BAX), B-cell lymphoma 2 (BCL-2) and Caspase 3 (CASP3) were determined at this concentration combination by RT-qPCR and ELISA methods, respectively. And the results showed that this combination inactivates the intrinsic apoptotic pathway in the PC-9 cell line.