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土木香内酯增效替莫唑胺抑制胶质瘤干细胞增殖的分子机制

Molecular Mechanism of Alantolactone Synergistic Temozolomide Inhibiting Glioma Stem Cell Proliferation
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摘要 目的:研究土木香内酯(ALT)联合替莫唑胺(TMZ)对胶质瘤干细胞增殖的作用及其机制。方法:取人胶质瘤细胞U87MG、U251MG进行培养,ALT、TMZ单独或联合干预。使用MTT检测细胞增殖情况,流式细胞术检测细胞凋亡情况,蛋白免疫印迹法(Western blot)检测凋亡通路蛋白Cleaved-caspase-9、Caspase-9、Bcl-2和Bcl-xl等表达量。结果:ALT和TMZ联合使用后胶质瘤干细胞生存率明显低于单独用药组差异有统计学意义(P<0.05);ALT和TMZ联合使用后胶质瘤干细胞凋亡比例明显高于单独用药组,差异有统计学意义(P<0.05);与单独使用TMZ相比,ALT与TMZ联合使用后,促凋亡蛋白Cleaved-caspase-9明显增强,抑凋亡蛋白Bcl-2和Bcl-xl明显降低,差异有统计学意义(P<0.05)结论:ALT可增加TMZ抑制胶质瘤干细胞增殖的效果,且其主要通过上调促凋亡蛋白,下调抑凋亡蛋白实现。 Objective:To study the effect and mechanism of Alantolactone combined wit h Temozolomide on the proliferation of glioma stem cells.Method:Human glioma cells were cultured with U87MG and U251MG,and were interacted with Alantolactone and Temozolomide alone or in combination.Cell proliferation was detected by MTT.Apoptosis was detected by flow cytometry.The expressions of Cleavedcaspase-9,Caspase-9,Bcl-2 and Bcl-xl were detected by Western blot.Result:The survival rate of glioma stem cells was significantly lower than that of the control group(P<0.05).The apoptosis rate of glioma stem cells after the combination of Alantolactone and Temozolomide was significantly higher than that of the single drug group,and the difference was statistically significant(P<0.05).Compared with used alone for Temozolomide,the combination of Alantolactone and Temozolomide promote the apoptosis protein cleaved Caspase-9 enhanced obviously,suppression of apoptosis protein significantly lower the Bcl-2 and the Bcl-xl,the differences were statistically significant(P<0.05).Conclusion:ALT can increase the inhibitory effect of TMZ on the proliferation of glioma stem cells,which is mainly achieved by up-regulating apoptotic protein and down-regulating apoptotic protein.
作者 王迅 任彤 郭天林 WANG Xun;REN Tong;GUO Tianlin(Dalian Third People’s Hospital,Dalian 116033,China)
出处 《中国医学创新》 CAS 2019年第31期24-28,共5页 Medical Innovation of China
基金 辽宁省自然科学基金(20180550761) 大连市中医药相关科学研究计划项目(17Z1007)
关键词 土木香内酯 替莫唑胺 胶质瘤 干细胞 增殖 凋亡 Alantolactone Temozolomide Glioma Stem cell proliferation Apoptosis
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