槲皮素通过STAT通路抑制胶质瘤干细胞增殖促进其凋亡  

Quercetin inhibits proliferation and promotes apoptosis of glioma stem cells via the STAT pathway

作　　者：刘义锋[1] 张保朝[1] 温昌明[1] 闻公灵[1] 周国平[2] 张敬伟[3] 贺海发 汪宁[1] 李巍[5] Liu Yi-feng Zhang Bao-chao Wen Chang-ming Wen Gong-ling Zhou Gou-ping Zhang Jing-wei He Hai-fa Wang Ning Li Wei(Department of Neurology Department of Neurosurgery Department of Oncology Department of Pathology, Nanyang Central Hospital Affiliated to Zhengzhou University, Nanyang 473000, Henan Province, China Department of Neurology, General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China)

机构地区：[1]郑州大学附属南阳中心医院神经内科,河南省南阳市473000 [2]郑州大学附属南阳中心医院神经外科,河南省南阳市473000 [3]郑州大学附属南阳中心医院肿瘤内科,河南省南阳市473000 [4]郑州大学附属南阳中心医院病理科,河南省南阳市473000 [5]解放军沈阳军区总医院神经内科,辽宁省沈阳市110016

出　　处：《中国组织工程研究》2017年第5期657-662,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(青年科学基金项目)(81401097)~~

摘　　要：背景:多项研究表明,槲皮素可抑制肿瘤细胞的增殖、迁移并促进其凋亡。目的:探索槲皮素对胶质瘤干细胞增殖及凋亡的影响。方法:采用免疫磁珠分离培养胶质瘤干细胞,分4组培养,分别以含0(对照),25,50,100μmol/L槲皮素的培养基培养。48 h后,MTT法检测细胞增殖,流式细胞仪检测细胞凋亡,Western blot检测增殖相关蛋白增殖细胞核抗原、凋亡相关蛋白Bcl-2、Bax和存活素及STAT3、p-STAT3的表达。结果与结论:(1)与对照组比较,槲皮素呈剂量依赖性抑制胶质瘤干细胞的增殖(P<0.05);随着槲皮素浓度的升高,胶质瘤干细胞增殖细胞核抗原表达逐渐降低;(2)与对照组比较,槲皮素呈剂量依赖性促进胶质瘤干细胞的凋亡(P<0.05);随着槲皮素浓度的升高,胶质瘤干细胞促凋亡蛋白Bax表达逐渐升高,抑制凋亡蛋白Bcl-2和存活素表达逐渐降低;(3)随着槲皮素浓度的升高,胶质瘤干细胞p-STAT3表达逐渐降低,STAT3表达无明显变化;(4)结果表明,槲皮素可能通过抑制STAT通路抑制胶质瘤干细胞的增殖,促进其凋亡。BACKGROUND： Several studies have reported that quercetin can inhibit the proliferation and migration but promotes apoptosis of tumor cells.OBJECTIVE： To explore the effect of quercetin on the proliferation and apoptosis of glioma stem cells and the signal pathway involved. METHODS： Glioma stem cells were isolated by immunomagnetic beads and treated in culture medium containingdifferent concentrations of quercetin（0, 25, 50, 100 μmol/L）. Cell proliferation was measured by MTT and apoptosis measured by flow cytometry at 48 hours after culture. The expression levels of Bcl-2, Bax and survivin, which are related to apoptosis, were detected by western blot. The expression of proliferating cell nuclear antigen（PCNA）, which is related to proliferation, was also detected by western blot. The expression of STAT3 and p-STAT3 was also determined by western blot. RESULTS AND CONCLUSION：（1） Compared with the control（0 μmol/L） group, quercetin inhibited the proliferation of glioma stem cells in a dose-depended manner（P〈0.05）. With the increase of the concentration of quercetin, the expression of PCNA was increased（P〈0.05）.（2） Quercetin induced apoptosis of glioma stem cells dose-dependently（P〈0.05）. With the increase of the concentration of quercetin, the expression of Bcl-2 and survivin was decreased, while the expression Bax was increased.（3） Quercetin could also inhibit phosphorylation of STAT3 dose-dependently, but the level of STAT3 was not changed. To conclude, these results show that quercetin could inhibit the proliferation of glioma stem cells and promote apoptosis via the STAT pathway.

关 键 词：中草药 肿瘤干细胞 细胞增殖 细胞凋亡 组织工程 干细胞 槲皮素 胶质瘤干细胞 增殖 凋亡 STAT通路 国家自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]