The interactive effect of amlodipine and chemotherapeutic agents in lung cancer cells

Chemoresistance is one of the major challenges in lung cancer treatment. The identification of new chemotherapeutic therapies with increased efficacy and minimal toxicity over those currently in use is a key area of current research. Calcium channel blockers are emerging as anticancer agents in lung and other cancers. This study evaluates the ability of amlodipine to sensitize non-small cell lung cancer (NSCLC) cells to the first-line chemotherapeutics used in lung cancer treatment. Cell viability in the presence of carboplatin, gemcitabine, pemetrexed, or paclitaxel alone or combined with amlodipine was evaluated in A549 and H1299 NSCLC cell lines using the colorimetric MTT cell proliferation assay. Nonlinear regression curve fit analyses were used to calculate half-maximal inhibitory concentrations (IC₅₀). Sensitization was estimated by the ratio of the IC₅₀ of the monotherapy to the IC₅₀ of the combined therapy that included that drug (R-value). We found that amlodipine significantly reduced cell viability in a dose-dependent manner, with IC₅₀ values of 23 and 25.66 μM in A549 and H1299 NSCLC cells, respectively. In addition, amlodipine combined with carboplatin, gemcitabine, pemetrexed, or paclitaxel had a significant sensitization effect on A549 and H1299 NSCLC cells compared to their single-drug treatments (R > 1.0). Our findings confirm the ability of amlodipine to sensitize NSCLC cells to first-line chemotherapy treatments.