Synergistic Anticancer Effects of Gemcitabine and Resveratrol on A549 Non-Small Cell Lung Cancer Cell Line

Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality worldwide. Gemcitabine is an established effective agent in the treatment of NSCLC. However, resistance and dose-dependent toxicity limit the clinical efficacy of gemcitabine. Resveratrol, a polyphenolic compound, has been proposed as a chemosensitizing agent capable of modulating multiple survival pathways. Objective: To assess whether resveratrol enhances the anticancer activity of gemcitabine in A549 NSCLC cells. Methods: The viability of A549 cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The synergistic interaction was analyzed using a constant molar ratio of 1:75 (gemcitabine: resveratrol). The combination index (CI) and dose reduction index (DRI) values were calculated across multiple effect levels. To see how the combination changed the ability of cells to divide and migrate, we used the clonogenic and wound-healing assays, respectively. Results: The data showed that combining gemcitabine and resveratrol increased cytotoxicity compared to using either drug alone. This was shown by CI values that were consistently below 1.0 for all effect levels that were tested. The DRI values for both drugs were greater than 1.0 at all the effect levels, suggesting dose-sparing potential. In addition, the combination significantly decreased the colony formation and cell migration compared with individual drug treatments. Conclusion: Resveratrol potentiated the anticancer effects of gemcitabine in A549 cells via synergistic cytotoxicity and enhanced suppression of the clonogenic survival and migratory potential.