白花前胡甲素联用低浓度紫杉醇对卵巢癌细胞紫杉醇耐药株A2780/TAX的作用研究  

Study on the effects of praeruptorin A combined with low concentration of taxol on taxol-resistant ovarian cancer cell line A2780/TAX

作　　者：陈秋荷 刘晓玲[1] 潘立行[1] 欧阳健敏 CHEN Qiu-he;LIU Xiao-ling;PAN Li-xing;OUYANG Jian-min(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangdong Guangzhou 510006,China)

机构地区：[1]广州中医药大学中药学院,广东广州510006

出　　处：《中国医院药学杂志》2022年第17期1755-1759,1765,共6页Chinese Journal of Hospital Pharmacy

基　　金：广东省中医药局面上项目(编号:20221117)。

摘　　要：目的:探讨白花前胡甲素(praeruptorin A,PA)增强卵巢癌A2780/TAX细胞对紫杉醇化疗敏感性的作用及机制,为卵巢癌的减毒增敏治疗提供新思路。方法:体外培养A2780/TAX细胞,分组(对照组、紫杉醇组、PA组、PA+紫杉醇组)干预;噻唑蓝溴化四唑(MTT)法检测细胞活力;乳酸脱氢酶(LDH)细胞毒性检测法检测细胞毒性;克隆形成实验评价细胞增殖能力;流式细胞术Annexin V-FITC/PI双染法检测细胞凋亡情况;蛋白免疫印迹实验检测Bax、Bcl-2、Cleaved Caspase 3、Caspase 3、Cleaved PARP、PARP及MMP9、MMP2的蛋白表达水平;划痕实验检测细胞迁移情况。结果:PA与低浓度紫杉醇联用显著抑制A2780/TAX细胞活力和增殖能力;流式细胞术Annexin V-FITC/PI双染结果显示,联用组的细胞凋亡率显著高于紫杉醇单用组;蛋白免疫印迹结果显示,与对照组、紫杉醇组相比,PA与低浓度紫杉醇联用能显著降低Bcl-2、Caspase 3、PARP、MMP9、MMP2蛋白表达量,提高Bax、Cleaved Caspase 3和Cleaved PARP蛋白水平;划痕实验结果显示,PA与低浓度紫杉醇联用能抑制A2780/TAX细胞迁移。结论:PA与低浓度紫杉醇联用可抑制A2780/TAX细胞活力和增殖能力,诱导细胞凋亡,并通过下调MMP9和MMP2表达抑制细胞迁移。OBJECTIVE To explore the effects and mechanism of praeruptorin A(PA)on the sensitivity of ovarian cancer A2780/TAX cells to taxol,so as to provide new idea for the treatment of ovarian cancer.METHODS A2780/TAX cells cultured in vitro were divided into four groups(control,taxol,PA,PA+taxol).Cell viability was detected by MTT assay.Cytotoxicity was detected by lactic dehydrogenase(LDH)cytotoxicity assay.Cell proliferation ability was evaluated by clone formation assay.Flow cytometric Annexin V-FITC/PI co-staining assay was conducted for cell apoptosis detection.The expression levels of Bax,Bcl-2,Cleaved Caspase 3,Caspase 3,Cleaved PARP,PARP,MMP9 and MMP2 were detected by Western blotting assay.Cell migration was detected by wound healing test.RESULTS PA combined with low concentration of taxol could significantly inhibit the viability and proliferation ability of A2780/TAX cells.Flow cytometry results indicated that the combined group of PA and taxol could greatly induce A2780/TAX cells apoptosis when compared with taxol group.The results of Western blotting assay revealed that PA combined with low concentration of taxol could obviously decrease the expression of Bcl-2,Caspase 3,PARP,MMP9 and MMP2,as well as up-regulating the protein levels of Bax,Cleaved Caspase 3 and Cleaved PARP.The result of wound healing assay showed that PA combined with low concentration of taxol could inhibit the migration of A2780/TAX cells.CONCLUSION PA combined with low concentration of taxol inhibits the viability and proliferation ability of A2780/TAX cells,induces the apoptosis,and inhibits the cell migration by down-regulating the expression of MMP9 and MMP2 proteins.

关 键 词：白花前胡甲素 紫杉醇 卵巢癌 A2780/TAX细胞 化疗敏感性 

分 类 号：R966[医药卫生—药理学]