通关藤注射液通过调控ATF3表达对紫杉醇抗乳腺癌细胞的增效作用  

Synergistic effect of Tongguanteng Injection and paclitaxel on breast cancer cells via regulating ATF3 expression

作　　者：张葳 陈君君 杨姣[2] 石美智 姜波 周丽 孔欠文 韩永龙[2] ZHANG Wei;CHEN Jun-jun;YANG Jiao;SHI Mei-zhi;JIANG Bo;ZHOU Li;KONG Qian-wen;HAN Yong-long(College of Food Sciences and Technology,Shanghai Ocean University,Shanghai 201306,China;Department of Pharmacy,The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University,Shanghai 200233,China)

机构地区：[1]上海海洋大学食品学院,上海201306 [2]上海交通大学附属第六人民医院药剂科,上海200233

出　　处：《中成药》2022年第6期1774-1782,共9页Chinese Traditional Patent Medicine

基　　金：国家自然科学基金资助项目(81773949,82003987);上海市自然科学基金资助项目(20ZR1442400);上海市卫生和计划生育委员会中医药科研课题(2018YP003);上海市浦东新区科技发展基金民生科研专项资金项目(PKJ2020-Y08)。

摘　　要：目的 探讨ATF3介导的通关藤注射液增强紫杉醇抗乳腺癌的作用机制。方法 体外培养人乳腺癌MDA-MB-231细胞,siRNA干扰ATF3的表达,给予通关藤注射液和紫杉醇单独或联合干预。采用RT-qPCR和Western blot法分别检测ATF3及相关细胞因子CCL2、TNF-α的表达,细胞划痕实验和Transwell实验检测细胞迁移和侵袭能力,Hoechst活细胞染色和流式细胞术检测细胞凋亡情况。结果 在ATF3-siRNA干扰的MDA-MB-231细胞中,紫杉醇可上调ATF3 mRNA和蛋白表达及细胞因子CCL2、TNF-α mRNA表达(P<0.05);而通关藤注射液有抵消紫杉醇引起的ATF3 mRNA和蛋白表达升高的趋势,可抵消细胞因子CCL2、TNF-α mRNA表达的上调(P<0.01)。通关藤注射液可抑制MDA-MB-231细胞的增殖和转移、诱导细胞凋亡,并且联合紫杉醇组的作用更为显著(P<0.01)。结论 通关藤注射液联合紫杉醇可能通过调控ATF3及相关细胞因子的表达,抑制乳腺癌细胞的增殖、转移、侵袭,促进乳腺癌细胞的凋亡,从而发挥增效作用。AIM To investigate the mechanism of ATF3-mediated enhancement of paclitaxel in the combat of breast cancer due to the involvement of Tongguanteng Injection.METHODS Upon human breast cancer MDA-MB-231 cells cultured in vitro,interferences of ATF3 expression with siRNA,and regimes of Tongguanteng Injection,paclitaxel,and their combination use were made respectively.The expressions of ATF3 and related cytokines CCL2 and TNF-α were detected by RT-qPCR and Western blot,respectively.The cells had their migration and invasion abilities detected by cell scratch test and Transwell test,and their apoptosis determined by Hoechst staining and flow cytometry.RESULTS In MDA-MB-231 cells interfered by ATF3-siRNA,paclitaxel up-regulated mRNA and protein expressions of ATF3 as well as the mRNA expressions of cytokines CCL2 and TNF-α(P<0.05).However,Tongguanteng Injection tended to offset not only the paclitaxel-induced increases in ATF3 mRNA and protein expressions,but also the increases in cytokine CCL2 and TNF-α mRNA expressions(P<0.01).Tongguanteng Injection inhibited the proliferation and metastasis of MDA-MB-231 cells,and induced apoptosis,and its combination use with paclitaxel produced an even more significant efficacy(P<0.01).CONCLUSION The combination use of Tongguanteng Injection and paclitaxel may exert a synergistic effect in the combat against breast cancer due to promotion of apoptosis,inhibition of the proliferation,metastasis and invasion of breast cancer cells via regulating the expressions of ATF3 and related cytokines.

关 键 词：通关藤注射液 乳腺癌 MDA-MB-231细胞 紫杉醇 ATF3 CCL2 TNF-Α 

分 类 号：R285.5[医药卫生—中药学]