The synergistic effect of resveratrol in combination with cisplatin on apoptosis via modulating autophagy in A549 cells

作者：Song Hu, Xiaolin Li, Rongrong Xu, Lingyun Ye, Hui Kong, Xiaoning Zeng, Hong Wang, Weiping Xie · 发表于：Acta Biochimica et Biophysica Sinica · 年份：2016 · DOI：10.1093/abbs/gmw026 · 被引用次数：72 · 研究领域：Sirtuins and Resveratrol in Medicine、Autophagy in Disease and Therapy、Calcium signaling and nucleotide metabolism

Several studies have shown that combination treatment with natural products and chemotherapy agents can improve the sensitivity and cytotoxicity of chemotherapy agents. Resveratrol, a natural product, has many biological effects including antitumor and antiviral activities, as well as vascular protective effect. The aim of this study is to investigate the synergistic anticancer effect of resveratrol in combination with cisplatin and the potential anticancer mechanisms involved in A549 cells. The results obtained from Cell Counting Kit-8 and isobolographic analysis demonstrated that combination of resveratrol and cisplatin resulted in synergistic cytotoxic effects in A549 cells. Results from Hoechst staining, flow cytometry and western blot analysis suggested that resveratrol enhanced cisplatin-mediated apoptosis. Meanwhile, the changes of LC3-II and P62 levels and formation of autophagosome suggested that resveratrol in combination with cisplatin triggered autophagy. More importantly, inhibiting autophagy by 3-methyladenine markedly attenuated the apoptosis caused by combination of resveratrol and cisplatin in A549 cells. Taken together, our study provides the first evidence that resveratrol combined with cisplatin synergistically induce apoptosis via modulating autophagic cell death in A549 cells. These findings also help us to understand the role of natural products in combination with chemotherapy agents in lung cancer.