p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy
p8 attenuates the apoptosis induced by dihydroartemisinin in cancer cells through promoting autophagy
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DOI：
10.1080/15384047.2015.1026477
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发表时间：
2015-05-01
影响因子：
3.6
通讯作者：
Zhou, Hui-Jun
中科院分区：
文献类型：
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作者：
Chen, Sang-Sang;Hu, Wei;Zhou, Hui-Jun
双氢青蒿素（DHA）在多种癌细胞中表现出抗癌活性，但单独的DHA对癌症治疗不够有效。本研究发现，DHA处理后，几种癌细胞的应激调节蛋白p8明显增加，这进一步通过上调内质网应激相关蛋白ATF4和CHOP诱导自噬。此外，当我们在癌细胞中通过siRNA沉默p8时，DHA诱导的凋亡显著增加，而癌细胞中p8的过表达导致对DHA诱导的凋亡的抵抗。此外，我们发现氯喹（CQ）抑制自噬可以增强DHA在体外和体内的抗癌作用。总之，我们发现p8介导的自噬减弱DHA诱导的癌细胞凋亡，这为使用p8作为癌症治疗靶点提供了证据，并表明DHA和自噬抑制剂的联合治疗可能是一种有效的癌症治疗策略。
Dihydroartemisinin (DHA) exhibits anticancer activities in a variety of cancer cells, but DHA alone are not effective enough for cancer therapy. In this study we found the stress-regulated protein p8 was obviously increased after DHA treatment in several cancer cells, which further to induce autophagy by the upregulation of endoplasmic reticulum stress-related protein ATF4 and CHOP. Furthermore, when we silenced p8 by siRNA in cancer cells, the apoptosis induced by DHA were notably increased, whereas the overexpression of p8 in cancer cells leaded to the resistance to DHA-induced apoptosis. Moreover, we found the inhibition of autophagy with chloroquine (CQ) can enhance the anticancer effect of DHA both in vitro and in vivo. In conclusion, we found that p8-mediated autophagy attenuates DHA-induced apoptosis in cancer cells, which provides evidence to support the use p8 as a cancer therapeutic target, and suggests that the combination treatment with DHA and autophagy inhibitor might be an effective cancer therapeutic strategy.