Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells
Autophagy inhibition enhances antiproliferative effect of salinomycin in pancreatic cancer cells
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DOI：
10.1016/j.pan.2017.08.009
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发表时间：
2017-11-01
期刊：
影响因子：
3.6
通讯作者：
Nakamura, Masafumi
中科院分区：
文献类型：
--
作者：
Endo, Sho;Nakata, Kohei;Nakamura, Masafumi
背景：盐霉素对多种类型的恶性肿瘤具有细胞毒作用并诱导自噬。然而，还没有阐明盐霉素处理诱导的自噬是否具有保护作用或细胞毒性作用。我们研究了盐霉素是否影响胰腺癌细胞的自噬，以及盐霉素治疗诱导的自噬是否在这些cells.Methods中具有保护或细胞毒性作用：我们研究了盐霉素使用三种胰腺癌细胞系的效果。我们使用流式细胞术研究对增殖和CD 133阳性分数的影响。此外，我们监测盐霉素处理后的自噬活性的变化，使用荧光免疫染色，蛋白质印迹和流式细胞术。结果：盐霉素可抑制胰腺癌细胞的增殖，并呈浓度依赖性，同时可降低胰腺癌细胞的CD133阳性率。盐霉素以浓度依赖性方式增强这些细胞的自噬活性。自噬抑制使胰腺癌细胞对salinomycin.Conclusions更敏感：我们的数据提供了第一个证据表明，自噬诱导的盐霉素对胰腺癌细胞有保护作用。盐霉素、自噬抑制剂和抗癌药物相结合的新治疗策略有望成为胰腺癌治疗的一种新方法。(C)2017 IAP和EPC。Elsevier B.V.出版，保留所有权利。
Background: Salinomycin has cytotoxic effects on various types of malignancy and induces autophagy. However, it has not been clarified whether autophagy induced by salinomycin treatment has a protective or cytotoxic role. We investigated whether salinomycin affects autophagy in pancreatic cancer cells and whether autophagy induced by salinomycin treatment has a protective or cytotoxic role in these cells.Methods: We investigated the effect of salinomycin using three pancreatic cancer cell lines. We investigated effect on proliferation and the CD133 positive fraction using flow cytometry. In addition, we monitored the change in autophagic activity after salinomycin treatment using fluorescent immunostaining, western blotting, and flow cytometry. Finally, knockdown of ATG5 or ATG7 by siRNA was used to investigate the impact of autophagy inhibition on sensitivity to salinomycin.Results: Salinomycin suppressed the proliferation of pancreatic cancer cells in a concentration dependent manner, and reduced the CD133 positive fraction. Salinomycin enhanced autophagy activity in these cells in a concentration dependent manner. Autophagy inhibition made pancreatic cancer cells more sensitive to salinomycin.Conclusions: Our data provide the first evidence indicating that autophagy induced by salinomycin have a protective role in pancreatic cancer cells. A new therapeutic strategy of combining salinomycin, autophagy inhibitors, and anticancer drugs could hold promise for pancreatic cancer treatment. (C) 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.