Resveratrol Enhances Gemcitabine-Induced Apoptosis in A549 Non-Small Cell Lung Cancer Cells

Background: Lung cancer is the commonest cause of cancer related mortality. Non-small cell lung cancer (NSCLC) is the most prevalent kind of lung malignancies. Gemcitabine is a first line drug used in NSCLC. However, the therapeutic efficacy of gemcitabine is constrained by the drug resistance and toxicity. Resveratrol is a natural polyphenol with chemosensitizing properties, enhancing the antitumor effects of chemotherapy. Objectives: To investigate whether resveratrol potentiates the apoptotic effect of gemcitabine in A549 cells and the modulatory effects of gemcitabine- resveratrol combination on PI3K/Akt and STAT3 pathways. Methods: Exponentially growing A549 cells were treated with gemcitabine, resveratrol, or their combination. Annexin V-fluorescein isothiocyanate (Annexin V-FITC)/propidium iodide (PI) staining was used to measure apoptosis. The protein expression levels of phospho-Akt and phospho-STAT3 were quantified using Western blotting. Results: The results indicated that gemcitabine-resveratrol combination greatly increased the apoptosis in A549 cells compared with single drug treatments. Moreover, the co-treatment significantly reduced the expression levels of phospho-Akt and phospho-STAT3 compared to each drug alone. Conclusion: Resveratrol enhanced gemcitabine-induced apoptosis in A549 cells. Moreover, the combination treatment resulted in augmented suppression of both phospho-Akt and phospho-STAT3 expression. These findings suggest resveratrol as potential adjunct to gemcitabine to in the treatment of NSCLC.