科研之友
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摘要
The multikinase inhibitor sorafenib was the established systemic therapy proven to increase the overall survival of patients with advanced hepatocellular carcinoma (HCC). However, benefits for patients on this therapy were modest in clinical practice. Melatonin is known to exert antitumor effects in HCC cells, this study investigated whether and how melatonin enhances the anti-tumor effects of sorafenib. We found that co-administration of melatonin and sorafenib exhibited a synergistic cytotoxic effect on HepG2 and Bel-7402 cells. In addition, melatonin and/or sorafenib increased the expression levels of Bax, and decreased the expression levels of Bcl-2, suggesting that apoptosis was enhanced by a combination of melatonin and sorafenib. We also found that sorafenib increased autophagic activity obviously compared with the untreated cells, as demonstrated by an upregulation of LC3-II and down regulation of P62. However, autophagic activity induced by sorafenib was obviously decreased after the addition of melatonin. Furthermore, chloroquine (CQ), an autophagy inhibitor, significantly increased the cytotoxicity and pro-apoptosis effects of sorafenib alone or combined with melatonin compared with those in the absence of CQ. Our present results suggest that sorafenib combined with melatonin generates synergetic effects on hepatoma cell lines. Moreover, synergism can be enhanced by autophagy inhibition. These results suggest that combination treatment of sorafenib and melatonin might be a potential strategy for HCC.
- 出版日期2017
- 单位安徽医科大学
