Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin.
Inhibition of Autophagy by Deguelin Sensitizes Pancreatic Cancer Cells to Doxorubicin.
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Deguelin 抑制自噬使胰腺癌细胞对阿霉素敏感
DOI：
10.3390/ijms18020370
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发表时间：
2017-02-10
影响因子：
5.6
通讯作者：
Qin RY
中科院分区：
文献类型：
--
作者：
Xu XD;Zhao Y;Zhang M;He RZ;Shi XH;Guo XJ;Shi CJ;Peng F;Wang M;Shen M;Wang X;Li X;Qin RY
胰腺癌是全球第四大癌症死亡原因。此外，由于耐药性，胰腺癌患者从当前化疗方法中获得的益处有限。因此，胰腺癌患者迫切需要一种有效的治疗策略。 Deguelin 是一种天然化学预防药物，通过诱导细胞死亡在实体瘤中发挥有效的抗增殖活性。然而，这种活性的分子机制尚未完全阐明。在这里，我们证明德桂林在体外阻断胰腺癌细胞的自噬并诱导细胞凋亡。阿霉素诱导的自噬在胰腺癌细胞中发挥保护作用，氯喹抑制自噬或沉默自噬蛋白5可增强阿霉素诱导的细胞死亡。类似地，德桂林抑制自噬也使胰腺癌细胞系对阿霉素变得化学敏感。这些研究结果表明，鱼腥草素对胰腺癌具有有效的抗癌作用，并增强了阿霉素的抗癌作用。这些发现提供的证据表明，德桂林和阿霉素联合治疗是治疗胰腺癌的有效策略。
Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.