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二氢青蒿素联合替莫唑胺抑制胶质瘤细胞增殖和诱导凋亡

The research on dihydroartemisinin combined with temozolomide inhibits the proliferation and induces apoptosis of glioma cells
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摘要 目的 观察二氢青蒿素(DHA)联合替莫唑胺(TMZ)对胶质瘤细胞增殖和凋亡的影响。方法 细胞计数试剂盒(CCK-8)法检测细胞增殖和细胞活性;流式细胞仪检测细胞凋亡;免疫印迹检测凋亡相关蛋白。结果 DHA对4株胶质瘤细胞的半数抑制浓度(IC50)值分别是[U251MG:(4.87±0.08) μg/ml,U87MG :(5.10±0.11) μg/ml,SHG44:(7.75±0.18) μg/ml和A172:(10.57±0.81) μg/ml],U87MG作为后续实验对象,DHA+TMZ抑制U87MG细胞增殖,凋亡率为:对照组(3.05±1.78)%;DHA组(10.20±1.76)%;TMZ组(25.90±2.06)%;DHA+TMZ组(34.37±6.98)%,DHA+TMZ组诱导了最高量的凋亡,差异有统计学意义(t=38.221,P<0.01);DHA+TMZ组能下调丝裂原细胞外激酶(MEK)和细胞外信号调节蛋白激酶(ERK)蛋白磷酸化水平及上调肿瘤抑制因子p53表达;下调B细胞淋巴瘤/白血病-2(bcl-2)和髓样细胞白血病-1(Mcl-1)的蛋白表达,而对B细胞淋巴瘤/白血病-2相关X蛋白(bax)的表达没有影响。结论 DHA联合TMZ治疗能抑制U87MG细胞增殖和诱导凋亡,其机制可能与抑制ERK信号通路(Raf/MEK/ERK信号通路),启动线粒体凋亡途径有关。 Objective To investigate the effects of dihydroartemisinin combined with temozolomide on proliferation and apoptosis of glioma cells.Methods CCK-8 assay was used to detect cell proliferation and cell viability;Flow cytometry was used to detect cell apoptosis;Western blotting was used to detect apoptosis-related protein expression.Results The average 50% inhibitory concentration (IC50) of DHA for four glioma cells lines was [U251MG: (4.87±0.08) μg/ml, U87MG: (5.10±0.11) μg/ml, SHG44: (7.75±0.18) μg/ml and A172: (10.57±0.81) μg/ml, respectively], U87MG was selected as the object for next experiment. DHA+ TMZ is to inhibit U87MG cell proliferation, the apoptosis rate was control group (3.05±1.78)%;DHA group (10.20±1.76)%;TMZ group (25.90±2.06)%;DHA+ TMZ group (34.37±6.98)%, respectively. DHA+ TMZ induced the highest amount of apoptotic death, there were significant differences compared to control (t=38.221, P<0.01);The therapy of DHA combined with TMZ can down-regulate the protein phosphorylation level for mitogen extracellular kinase (MEK) and extracellular signal-regulated protein kinase (ERK) and up-regulate tumor suppressor p53;down-regulate Protein expression of B-cell lymphoma/leukemia-2 (bcl-2) and myeloid leukemia-1 (Mcl-1), but not B cell lymphoma/leukemia-2 related X (bax).Conclusion The therapy of DHA combined with TMZ can inhibit U87MG cell proliferation and induce apoptosis, which may be related to inhibition of ERK signaling pathway (Raf/MEK/ERK signaling pathway) and activation of the mitochondrial apoptosis pathway.
作者 严峻 文静 陈海南 黄乾荣 李希圣 莫立根 Yan Jun;Wen Jing;Chen Hainan;Huang Qianrong;Li Xisheng;Mo Ligen(Department of Neurosurgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning 530021, China;Department of Rheumatism, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China;Department of Neurosurgery, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China)
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2019年第2期274-276,共3页 Chinese Journal of Experimental Surgery
基金 广西高校中青年教师基础能力提升项目 (2017KY0489) 桂林市科技计划课题 (20170109-48) 广西中医药民族医药自筹经费科研课题 (GZZC16-53).
关键词 胶质瘤 二氢青蒿素 替莫唑胺 增殖 凋亡 Glioma Dihydroartemisinin Temozolomide Proliferation Apoptosis
作者简介 通信作者:莫立根,Email:ligenmo@163.com.
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