阿法替尼逆转人卵巢癌耐药A2780T细胞多药耐药性的作用研究  

Studies on the Reversal Effect of Afatinib on the Multidrug Resistance in Human Ovarian Cancer A2780T Cells

作　　者：李鹏翀 马丹宝 蔡洁莹 张韫琪 李国锋[3] LI Peng-chong;MA Dan-bao;CAI Jie-ying;ZHANG Yun-qi;LI Guo-feng(Department of Pharmacy,The People′s Hospital of Nanhai District,Foshan 528000,China;School of Basic Medical Science,Guangzhou University of Chinese Medicine,Guangzhou 501515,China;Department of Pharmacy,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]南海区人民医院药学科,广东佛山528000 [2]广州中医药大学基础医学院,广东广州510006 [3]南方医科大学南方医院药学部,广东广州510515

出　　处：《海峡药学》2020年第2期11-14,共4页Strait Pharmaceutical Journal

基　　金：广东省科技计划项目(2014A020212197)。

摘　　要：目的研究阿法替尼对人卵巢癌细胞A2780T体外增殖的影响及对多药耐药性(Multidrug resistance,MDR)逆转作用,以寻找新型的MDR逆转剂。方法采用MTT法考察阿法替尼对卵巢癌细胞A2780T的细胞毒性及其逆转耐药作用;流式细胞仪检测阿法替尼对A2780T细胞凋亡的影响。结果阿法替尼可浓度依赖性的显著降低紫杉醇对A2780T的IC50。与0.625μM(低)、1.25μM(中)及2.5μM(高)的阿法替尼联用时,紫杉醇对A2780T细胞的IC50分别为(115.53±6.65)μM、(19.74±1.19)μM及(8.86±0.72)μM,较未联用阿法替尼组紫杉醇的IC50分别显著下降了1.72倍、10.08倍及22.45倍(P<0.01)。阿法替尼逆转A2780T对紫杉醇的MDR效果,强于相同浓度的可逆性TKIs类药物拉帕替尼及10μM的维拉帕米。阿法替尼可浓度依赖性显著增加紫杉醇诱导的A2780T细胞的凋亡率(P<0.01)。结论低浓度阿法替尼能逆转人卵巢癌耐药A2780T细胞的MDR,具有作为MDR逆转剂的前景。OBJECTIVE This study was to observe the reversal effect of afatinib on the multidrug resistance in human ovarian cancer A2780 T cells.METHODS MTT assay was used to investigate the cytotoxicity of alfatinib on human ovarian cancer resistance A2780 T cells and its reversal effect.Apoptosis rate of A2780 T cells were analyzed by Flow cytometer.RESULTS Afatinib strongly decreased the IC50 values of paclitaxel in ABCB1-overexpressing A2780 T cells in a concentration-dependent manner.Afatinib at concentrations of 0.625μM,1.25μM and 2.5μM significantly decreased the IC50 values of paclitaxel in A2780 T cells by 1.72 folds,10.08 folds and 22.45 folds,respectively(P<0.01).The reversal effects of afatinib on MDR to paclitaxel in A2780 T cells were stronger than that of the same concentrations of lapatinib(reversible TKIs) or 10μM verapamil(a function inhibitor of ABCB1).Afatinib significantly increased the percentages of apoptosis induced by paclitaxel in multidrug-resistant A2780 T cells.CONCLUSION Alfaitidine can reverse the MDR of human ovarian cancer A2780 T cells,which may be an potential MDR reversal agent.

关 键 词：阿法替尼 卵巢癌 多药耐药性 逆转剂 

分 类 号：R965[医药卫生—药理学]