消癌平注射液调节核受体增强紫杉醇抑制卵巢癌A2780细胞增殖的机制  

Enhances of the Inhibitory Effect of Paclitaxel on the Proliferation of Ovarian Cancer A2780 Cell by Xiaoaiping Injection via Modulating Nuclear Receptors

作　　者：张湘奇[1] 陈君君 杨姣[1,2] 石美智 祁美娟 肖霄 王洪斌 韩永龙 ZHANG Xiangqi;CHEN Junjun;YANG Jiao;SHI Meizhi;QIMeijuan;XIAO Xiao;WANG Hongbin;HAN Yonglong(Departmentof Pharmacy, Shanghai Jiaotong University Affiliated the SixthPeople's Hospital, Shanghai 200233,China;Department of Pharmacy,Shanghai University of Medicine & Health Sciences Affiliated theSixth People's Hospital East Campus, Shanghai 201306,China;Collegeof Food Sciences & Technology, Shanghai Ocean University,Shanghai 201306,China;College of Pharmacy, California North State University, California CA95757, USA)

机构地区：[1]上海交通大学附属第六人民医院药剂科,上海200233 [2]上海健康医学院附属第六人民医院东院药剂科,上海201306 [3]上海海洋大学食品学院,上海201306 [4]北加州大学药学院,美国加利福尼亚ca95757

出　　处：《医药导报》2019年第6期693-700,共8页Herald of Medicine

基　　金：国家自然科学基金资助项目(81773949);上海市卫生和计划生育委员会科研课题青年项目(20174Y0023);上海健康医学院种子基金项目(HMSF-17-22-018;HMSF-17-22-020);浦东新区卫生计生科技项目(PW2017E-2);浦东新区民生科研专项资金(PKJ2017-Y07)

摘　　要：目的探讨消癌平注射液通过调节核受体PXR/CAR增强紫杉醇抑制卵巢癌A2780细胞增殖的作用机制。方法分别将20,40,80,160 mg·mL^(-1)消癌平注射液,10,40,80,160 nmol·L^(-1)紫杉醇单用,或两药联用于人卵巢癌细胞A2780细胞株,采用噻唑蓝(MTT)法检测药物对细胞的抑制率,倒置相差显微镜观察药物对细胞形态的影响,逆转录-聚合酶链反应(RT-PCR)法检测药物对PXR、CAR及下游药物代谢酶CYP2C8、CYP3A4、CYP3A5和转运体P-gp的mRNA表达的影响,Western blotting法检测药物对PXR、CYP2C8蛋白表达的影响。结果消癌平注射液处理卵巢癌A2780细胞后,细胞增殖受到抑制,且随药物浓度增加、作用时间延长,抑制率显著增加;与紫杉醇单用组比较,消癌平注射液联用紫杉醇后对细胞增殖的抑制作用更为显著;RT-PCR和Western blotting结果显示消癌平注射液可抑制紫杉醇激活的PXR及下游代谢酶CYP2C8的mRNA和蛋白的表达。结论消癌平注射液与紫杉醇联用能够增强紫杉醇对卵巢癌A2780细胞增殖的抑制作用,其机制可能与消癌平注射液抑制与药物代谢相关的核受体PXR和下游药物代谢酶CYP2C8表达有关。Objective To explore the mechanism of Xiaoaiping injection enhancing the inhibitory effect of paclitaxel on the proliferation of ovarian cancer cell A2780. Methods Ovarian cancer cell line A2780 were treated by Xiaoaiping injection (20,40, 80,160 mg·mL^-1 ) or paclitaxel(10,40,80,160 nmol·L^-1 ) or Xiaoaiping injection combined with paclitaxel, respectively. The inhibition ratios of different drugs on the proliferation of A2780 cells were measured by MTT method. The changes in cell morphology after drug treatment were monitored by microscope. The mRNA expression of PXR, CAR and CYP2C8, CYP3A4, CYP3A5, transporter P-gp were detected by RT-PCR. The protein expression of PXR, CYP2C8 were measured by Western blotting. Results Xiaoaiping injection inhibits the proliferation of A2780 cells in a time- and concentration-dependent manner. Compared with paclitaxel treatment alone, Xiaoaiping injection combined with paclitaxel exhibit more significant inhibitory effect on A2780 cell proliferation RT-PCR and Western blotting results revealed that Xiaoaiping injection can significantly inhibit paclitaxel-induced over expression of PXR and CYP2C8. Conclusion Xiaoaiping injection can significantly enhance the inhibitory effect of paclitaxel on the proliferation of ovarian cancer A2780 cells. The mechanism may be associated with the inhibitory effect of Xiaoaiping on paclitaxel-induced overexpression of nuclear receptor PXR and its downstream drug metabolic enzyme CYP2C8.

关 键 词：消癌平注射液 紫杉醇 孕烷X受体 药物代谢 CYP2C8酶 

分 类 号：R969.2[医药卫生—药理学] R737.31[医药卫生—药学]