APG-1252 enhances the anticancer role of paclitaxel in non-small-cell lung cancer cells by suppressing the extracellular regulated protein kinases/myeloid cell leukemia 1 pathway.

The efficacy of paclitaxel (PTX), an important chemotherapy drug in non-small-cell lung cancer (NSCLC) cells, is limited by its resistance. APG-1252 has an inhibitory role in cancer and can inhibit myeloid cell leukemia 1 (MCL-1) to enhance chemotherapy drugs' antitumor effect. Therefore, this research further investigated whether APG-1252 could enhance the anticancer role of PTX by regulating MCL-1. NSCLC cells were treated with drugs. Cell viability was determined using the cell counting kit-8 assay. The cell apoptosis was examined using flow cytometry and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling staining. The abilities of cells to migrate, invade, and proliferate were examined using transwell and colony formation assays, as needed. The expression levels of extracellular regulated protein kinases (ERK), phosphorylated ERK (p-ERK), and MCL-1 were quantified by Western blot. APG-1252 and PTX decreased the NSCLC cells' viability. APG-1252 and PTX induced cell apoptosis and inhibited the cells from migrating, proliferating, and invading. APG-1252 and PTX suppressed the expression of p-ERK and MCL-1. Besides, APG-1252 enhanced the anticancer role of PTX in NSCLC cells. Ro 67-7476, a p-ERK agonist, had an opposite role to the combination of APG-1252 with PTX in NSCLC cells. Additionally, Ro 67-7476 abolished the anticancer role of the combination of APG-1252 with PTX in the biological functions of NSCLC cells. APG-1252 enhanced the anticancer role of PTX in NSCLC cells by suppressing the ERK/MCL-1 pathway. This work provided the theoretical basis for the APG-1252 application.