小檗碱通过抑制ALDH1活性降低卵巢癌细胞药物转运蛋白的表达逆转紫杉醇耐药  

Berberine Reversing Paclitaxel Resistance by Inhibiting ALDH1 Activity and Reducing the Expression of Drug Transporter in Ovarian Cancer Cells

作　　者：宋涛涛 李梦一 袁冰凡 黄丽丽 Song Taotao;Li Mengyi;Yuan Bingfan;Huang Lili(Department of Pharmacy,Li Huili Hospital,Ningbo Medical Center,Zhe jiang Ningbo 315100 China;College of Basic Sciences,Anhui Medical University)

机构地区：[1]宁波市医疗中心李惠利医院药剂科,浙江宁波315100 [2]安徽医科大学基础学院

出　　处：《中国药师》2022年第7期1144-1150,共7页China Pharmacist

摘　　要：目的:深入探究小檗碱对紫杉醇耐药性卵巢癌细胞的体外活性影响及其机制。方法:将细胞使用DMSO(Control)、小檗碱组(Berberine)、紫杉醇(Paclitaxel)、紫杉醇+小檗碱(Combined)、HY-B0240(Inhibitor)、HY-B0240+小檗碱(HB)处理,24h后通过MTT法检测各组细胞增殖情况,Transwell检测各组细胞侵袭和迁移,流式细胞术分析细胞凋亡,Westernblot检测增殖、迁移、侵袭和凋亡相关蛋白的表达,并通过免疫荧光分析P-gp(P-糖蛋白)和ALDH1(乙醛脱氢酶1,Acetaldehydedehydrogenase1)的表达。结果:相较于对照组细胞,小檗碱组或联合用药组细胞增殖、迁移、侵袭被进一步抑制,细胞凋亡明显增加(P<0.05);与小檗碱组相比,小檗碱与ALDH1抑制剂联用后,ALDH1和P-gp蛋白、细胞表型和相关蛋白的表达无明显变化(P>0.05)。结论:小檗碱通过抑制ALDH1活性降低卵巢癌细胞药物转运蛋白的表达逆转紫杉醇耐药。Objective:To investigate the effects of berberine on the activity of paclitaxel-resistant ovarian cancer cells in vitro and its mechanism.Methods:The cells were respectively treated with DMSO(Control),berberine(Berberine),paclitaxel(Paclitaxel),paclitaxel+berberine(Combined),HY-B0240(Inhibitor)and HY-B0240+berberine(HB).After 24-hour treatment,cell proliferation was detected by MTT method,cell invasion and migration were detected by Transwell,apoptosis was analyzed by flow cytometry,and Western blot was used to detect the expression of proliferation,migration,invasion and apoptosis related proteins.The expression of P-gp(P-glycoprotein)and ALDH1(aldehyde dehydrogenase 1)was analyzed by immunofluorescence.Results:Compared with those in the control cells,the cell proliferation,migration and invasion were further inhibited after berberine or combined treatment,and the cell apoptosis was significantly increased(P<0.05).After berberine combined with ALDH1 inhibitor,ALDH1 and P-gp protein did not change significantly compared with those in berberine group,and the cell phenotype and the expression of related proteins did not change significantly(P>0.05).Conclusion:Berberine can reverse paclitaxel resistance by inhibiting ALDH1 activity and reducing the expression of drug transporter in ovarian cancer cells.

关 键 词：紫杉醇 卵巢癌 P-糖蛋白 乙醛脱氢酶 

分 类 号：R965.1[医药卫生—药理学]