从STAT3通路探讨桂枝茯苓丸对MCF-7细胞增殖的抑制作用机制  

Study on the inhibition mechanism of Guizhi Fuling pill on proliferation of MCF-7 cells from STAT3 pathway

作　　者：吴耀松[1] 夏雷达 张培旭 刘燕[1] 张文娴[1] 蒋时红[1] WU Yao-song;XIA Lei-da;ZHANG Pei-xu;LIU Yan;ZHANG Wen-xian;JIANG Shi-hong(Henan University of Chinese Medicine,Zhengzhou Henan,450008 china)

机构地区：[1]河南中医药大学,河南郑州450008

出　　处：《时珍国医国药》2018年第12期2904-2906,共3页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81503490);河南省教育厅重点项目(13A360582);河南省基础与前沿计划项目(132300410157)

摘　　要：目的探讨桂枝茯苓丸抑制乳腺癌MCF-7细胞增殖作用机制。方法采用MTT法检测高低剂量桂枝茯苓丸(1800g/m L、2700g/m L)及其与STAT3通路抑制剂AG490联合作用48h后对MCF-7细胞增殖抑制作用;流式细胞术检测细胞周期及细胞中STAT3、P-STAT3、Cyclin D1、P53表达的变化。结果与空白组比较,用药组抑制细胞增殖作用呈剂量依赖性,加阻断剂AG490联合用药组明显高于相对应的单独用药组。与空白对照组比较,AG490组G0/G1期细胞比例升高明显(P <0. 05),桂枝茯苓丸高、低剂量组及其联合用药组G0/G1期和S期细胞比例降低(P <0. 05)。与空白组比较,各组P-STAT3的表达都显著下调(P <0. 05),但各剂量组STAT3表达均无显著变化(P> 0. 05);除低剂量桂枝茯苓丸组无差异外,其它各组P53表达显著上调(P <0. 05);只有高剂量桂枝茯苓丸组及其与AG490联合组Cyclin D1表达显著下调(P <0. 05)。与相应剂量桂枝茯苓丸相比,加AG490阻断剂后,P-STAT3、Cyclin D1表达均下调明显,P53表达均上调明显。结论桂枝茯苓丸及STAT3通路AG490阻断剂能抑制MCF-7细胞生长,且呈剂量依赖性,其机理与药物调控P-STAT3、Cyclin D1的表达下调及蛋白P53表达上调有关。Objective To study the effect of Guizhi Fuling pill on the growth of MCF-7 cells from human breast cancer and the protein expression of STAT3,p-STAT3,cyclin D1,and p53,and to explore the mechanism of Guizhi Fuling pill on inhibiting the proliferation of MCF-7 breast cancer cells,and which provide a theoretical foundation in the clinical application.Methods The inhibitory effect of the high and low dose of Guizhi Fuling pill( 1800 g/m L、2700 g/m L) and its combination with the inhibitor AG490 of STAT3 pathway after 48 h on the proliferation of MCF-7 cell was detected by MTT. The cell of cycle and the changes of STAT3,p-STAT3,cyclin D1 and p53 expression in cells were study by flow cytometry. Results Compared with the blank group,the inhibitory effect of the drug group on cell was dose-dependent,and the group of inhibitor AG490 was significantly higher than the corresponding drug group. Compared with the blank group,the cells were blocked in G0/G1 phase mixed with AG490( P < 0. 05);and the ratio of G0/G1 and S phase could be decreased in the high,low concentration group of Guizhi Fuling pill and the its combined AG490 group( P < 0. 05). Compared with the blank group,the expression of p-STAT3 was significantly reduced( P < 0. 05),but no significant changes in the expression of STAT3 in each dose group;Except for the low dose of Guizhi Fuling pill group,the expression of p53 was significantly increased in other groups( P < 0. 05);Only the expression of cyclin D1 in the high dose of Guizhi Fuling pill group and its combined group with AG490 were significantly reduced( P <0. 05);After combining AG490,the expression of p-STAT3 and cyclin D1 were reduced significantly,and the expression of p53 was significantly increased compared with the same dose group of Guizhi Fuling pill( P < 0. 05). Conclusion Guizhi Fuling pill and the inhibitor AG490 of STAT3 pathway can inhibit the growth of MCF-7 cells,and is dose – dependent,which mechanism is related to the down-regulation of the expression of p-STAT3,cyclin D1 and the up

关 键 词：桂枝茯苓丸 MCF-7细胞 STAT3信号通路 CYCLIND1 P53 

分 类 号：R285.5[医药卫生—中药学]