异槲皮苷通过内质网应激/自噬途径诱导宫颈癌细胞凋亡的作用机制  

Mechanism of Isoquercitrin in Inducing Apoptosis of Cervical Cancer Cells Through Endoplasmic Reticulum Stress and Autophagy Pathways

作　　者：蔡颖 杨英捷[2] CAI Ying;YANG Yingjie(School of Obstetrics and Gynecology,Graduate School of Guizhou Medical University,Guiyang 550000,China;Gynecological Tumor Surgery of Guizhou Cancer Hospital,Guiyang 550000,China)

机构地区：[1]贵州医科大学研究生院,贵阳550000 [2]贵州省肿瘤医院妇瘤外科,贵阳550000

出　　处：《世界中医药》2022年第6期795-800,共6页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81601259)。

摘　　要：目的:研究异槲皮苷通过内质网应激和自噬途径诱导宫颈癌细胞凋亡的作用机制。方法:将SiHa细胞随机分为对照组、异槲皮苷低剂量组、异槲皮苷中剂量组和异槲皮苷高剂量组。异槲皮苷低、中、高剂量组细胞分别使用终浓度为20μmol/L、40μmol/L和80μmol/L的异槲皮苷培养,对照组细胞使用正常培养基培养。使用CCK-8分别在24 h、48 h和72 h检测细胞增殖情况;EDU检测各组细胞在72 h时的增殖情况;荧光定量PCR检测各组细胞内质网应激相关mRNA的表达;Western Blotting检测各组细胞蛋白表达情况;流式细胞术检测细胞凋亡情况。结果:与对照组细胞比较,低、中、高剂量异槲皮苷作用后,细胞OD值均明显降低;葡萄糖调节蛋白78 mRNA、CHOP mRNA以及葡萄糖调节蛋白78蛋白、C/EBP同源蛋白质(CHOP)、胱天蛋白酶12蛋白、Beclin 1蛋白、Bax蛋白、Cl-胱天蛋白酶-3蛋白表达水平以及LC3Ⅱ/LC3Ⅰ比值均明显升高;P62蛋白、Bcl-2蛋白、p-JAK2蛋白和p-信号转导及转录激活蛋白3表达水平均明显降低;细胞凋亡率明显升高,差异有统计学意义(P<0.05)。且异槲皮苷的作用呈剂量依赖性。结论:异槲皮苷可通过内质网应激途径和自噬途径,诱导宫颈癌细胞凋亡。Objective:To explore the mechanism of isoquercitrin in the induction of apoptosis in cervical cancer cells through endoplasmic reticulum stress and autophagy pathways.Methods:The SiHa cells were randomly divided into a control group,and low-(20μmol/L),medium-(40μmol/L),and high-dose(80μmol/L)isoquercitrin groups.The cells in the isoquercitrin groups were cultured with corresponding drugs,and those in the control group with normal medium.The cell proliferation was detected at 24 h,48 h,and 72 h using CCK-8 kits.EDU was used to detect the proliferation of cells in each group at 72 h.The expression of endoplasmic reticulum stress-related genes was detected by qRT-PCR.The protein expression in each group was detected by Western blot.Cell apoptosis was detected by flow cytometry.Results:Compared with the control group,the isoquercitrin groups showed reduced OD values in cells,increased expression levels of glucose-regulated protein 78(GRP78)mRNA,CHOP mRNA,GRP78 protein,CHOP protein,Caspase-12 protein,Beclin 1 protein,Bax protein,Cl-caspase-3 protein,and the LC3Ⅱ/LC3Ⅰratio,decreased expression levels of p62 protein,Bcl-2 protein,p-JAK2 protein,and p-STAT3 protein,and elevated apoptosis rate(P<0.05).The effect of isoquercitrin was in a dose-dependent manner.Conclusion:Isoquercitrin can induce apoptosis of cervical cancer cells through endoplasmic reticulum stress and autophagy pathways.

关 键 词：异槲皮苷 宫颈癌 内质网应激 增殖 自噬 凋亡 JAK/信号转导及转录激活蛋白信号通路 

分 类 号：R284[医药卫生—中药学] R737.33[医药卫生—中医学]