4'-甲醚-黄芩素对耐药性人绒毛膜癌的耐药逆转作用  

Reversal effect of 4'-methylether-scutellarein on multidrug resistance of human choriocarcinoma

作　　者：李卓[1,2] 朱利群[2] 张燕[2] 徐昌芬[2] 徐珊[2] 

机构地区：[1]西安医学院第一附属医院检验科,陕西西安710077 [2]南京医科大学基础医学院细胞生物学教研室,江苏南京210029

出　　处：《中国肿瘤生物治疗杂志》2016年第2期182-187,共6页Chinese Journal of Cancer Biotherapy

基　　金：陕西省教育厅专项科研计划项目(No.12JK0768);江苏省高校自然科学基金资助项目(No.06KJB360067)~~

摘　　要：目的:研究4'-甲醚-黄芩素(4'-methylether-scutellarein,4'-M-S)对耐药性人绒毛膜癌的体内耐药逆转作用并探讨其相关作用机制。方法:在BALB/c裸鼠左侧腋窝皮下注射耐药性人绒毛膜癌细胞JAR/VP-16建立耐药性人绒毛膜癌裸鼠皮下移植瘤模型,瘤体直径至1.0 cm时,随机分为空白对照组、依托泊苷(etoposide,VP16)化疗组、4'-M-S组和4'-M-S+VP16联合治疗组,每组10只荷瘤鼠。动态观测各治疗组荷瘤鼠肿瘤生长情况,并记录存活时间。治疗3周后,通过光镜、透射电镜观察移植瘤组织形态学改变,流式细胞术检测移植瘤细胞凋亡率的变化,用RT-PCR、Western blotting检测并比较4组移植瘤组织中多药耐药基因1(multidrug resistance 1,MDR1)mRNA、肺耐药相关蛋白(lung resistance-related protein,LRP)mRNA及其产物P-糖蛋白(permeability-glycoprotein,P-gp)和LRP的表达情况。结果:治疗3周后发现,4'-M-S对耐药性人绒毛膜癌有一定的体内抑制作用,与VP16联合用药可使裸鼠移植瘤生长明显受抑,抑瘤率达48.21%,同时可减轻化疗毒性反应、明显改善荷瘤鼠生活质量,并显著延长其平均存活时间;与其他3组相比,4'-M-S+VP16联合治疗组移植瘤细胞凋亡率显著升高(均P<0.05),移植瘤组织中MDR1 mRNA、LRP mRNA及其编码蛋白P-gp和LRP表达水平均显著下降(均P<0.05)。结论:4'-M-S能有效逆转人绒毛膜癌对化疗药物VP16的耐药性,其机制可能与4'-M-S诱导细胞凋亡和下调耐药基因MDR1 mRNA、LRP mRNA及相应产物P-gp和LRP的表达有关。Objective： To evaluate the reversal effect of 4＇-methylether-scutellarein（ 4＇-M-S） on multidrug resistance of human choriocarcinoma in vivo,and investigate its mechanism. Methods： Drug resistant human choriocarcinoma cells were subcutaneously injected into left armpits of BALB / c nude mice to construct the subcutaneous exnograft model. When diameter of the xenografts reached 1. 0 cm,the mice were randomly divided into four groups with ten mice in each,namely control grop,etoposide（ VP16） group,4＇-M-S group and 4＇-M-S ＋ VP16 group. After the treatment for three weeks,growths of the exnograft tumors were dynamically observed and survival times of the mice recorded in the various groups,morphological changes of the tumor tissues were observed with optical and transmission electron microscopes and apoptosis rates of the exnograft cells detected with flow cytometry assay. Expression levels of MDR1 mRNA,LRP mRNA and their coding proteins,P-gp and LR,were detected and compared among the four groups with RT-PCR and Western blotting assays respectively. Results： After the treatments for three weeks,it was found that 4＇-M-S has somewhat inhibitory effect on drug-resistant human choriocarcinoma in vivo,4＇-M-S ＋ VP16 could apparently inhibit growth of the exnograft tumors in the nude mice with inhibition rate of 48. 21%. Meanwhile,toxicity of the chemotherapy was reduced,life quality of mice with the exnograft tumors obviously improved and their mean survival times significantly prolonged. In the 4＇-M-S ＋ VP16 group,apoptosis rate of the xenograft cells was significantly increased,and expression levels of MDR1 mRNA,LRP mRNA and their coding proteins,P-gp and LR,in the exnograft tumors significantly decreased comparing with the other three groups（ all P〈0. 05）. Conclusion： 4＇-M-S could effectively reverse resistance of the human choriocarcinoma to the chemotherapy drug VP16,which might be related with 4＇-M-S inducing apoptosis of the tumor cells and down-regulating expression of

关 键 词：绒毛膜癌 多药耐药 裸鼠 多药耐药逆转 4'-甲醚-黄芩素 依托泊苷 

分 类 号：R737.33[医药卫生—肿瘤]