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双氢青蒿素通过靶向 Janus 激酶 2/信号转导及转录激活因子 3 信号通路增加结肠癌细胞的凋亡。

Dihydroartemisinin increases apoptosis of colon cancer cells through targeting Janus kinase 2/signal transducer and activator of transcription 3 signaling.

作者信息

Wang Dongsheng, Zhong Bei, Li Yu, Liu Xiaodong

机构信息

Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Department of Hyperbaric Oxygen, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1949-1954. doi: 10.3892/ol.2017.7502. Epub 2017 Nov 29.

DOI:10.3892/ol.2017.7502
PMID:29434895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5776939/
Abstract

As a derivative of artemisinin, dihydroartemisinin is effective in the treatment of malaria. Dihydroartemisinin has been identified to possess inhibitory effects in numerous types of animal model with tumors, indicating that it has an antineoplastic effect. The aim of the present study was to analyze the potential anticancer effects of dihydroartemisinin, particularly its effect on apoptosis of colon cancer cells. In the present study, it was identified that dihydroartemisinin inhibited cell viability, promoted cell apoptosis, increased B-cell lymphoma-2-associated X-protein expression, increased caspase-3/9 activities, decreased poly(ADP-ribose) polymerase levels, decreased phosphorylation of extracellular-signal-regulated kinase, and increased phosphorylation of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase in colon cancer cells. Conversely, the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) was suppressed by dihydroartemisinin in colon cancer cells. These results demonstrate that the potential anticancer effects of dihydroartemisinin may increase apoptosis of colon cancer cells through targeting JAK2/STAT3 signaling.

摘要

作为青蒿素的衍生物,双氢青蒿素在疟疾治疗中具有疗效。双氢青蒿素已被证实对多种肿瘤动物模型具有抑制作用,表明其具有抗肿瘤作用。本研究的目的是分析双氢青蒿素的潜在抗癌作用,特别是其对结肠癌细胞凋亡的影响。在本研究中,发现双氢青蒿素抑制结肠癌细胞的活力,促进细胞凋亡,增加B细胞淋巴瘤-2相关X蛋白表达,增加半胱天冬酶-3/9活性,降低聚(ADP-核糖)聚合酶水平,降低细胞外信号调节激酶的磷酸化,并增加c-Jun氨基末端激酶和p38丝裂原活化蛋白激酶的磷酸化。相反,双氢青蒿素在结肠癌细胞中抑制了Janus激酶2(JAK2)和信号转导及转录激活因子3(STAT3)的磷酸化。这些结果表明,双氢青蒿素的潜在抗癌作用可能通过靶向JAK2/STAT3信号通路增加结肠癌细胞的凋亡。

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