罗格列酮逆转丝裂霉素对人胃癌 SGC7901／VCR祼鼠移植瘤耐药作用的研究

摘要

Objective To explore the effect of rosiglitazone( ROS) ,a selective peroxisome proliferator-activated receptor gamma ( PPARγ) ligand,reverses Mitomycin C resistance on nude mice xenografts of human gastric cancer SGC7901/VCR cells and its possible mechanism.Methods The model of xenografts tumor in nude mice were established by inoculating human gastric cancer SGC7901/VCR cells into the back of nude mice subcutaneously.48 male nude mice were divided into 6 groups:Control group,MMC group,ROS group,MMC combined moderate dose ROS group,MMC combined high dose ROS group,MMC combined cyclosporineA( CSA) group.There were 8 mice in each group.After treated for 40 days,the volumes changes of tumor and tumor inhibition rates were observed,draw the growth curve of xenograft tumor.The expression of P-glycolprotein( P-gp) and MGr1-Ag were observed with Western-blot assay respectively.Results After medication the effect on the volume of tumor and tumor inhi-bition rates:there was no significant difference between the control group and MMC group(P>0.05),the difference of tumors volume and tumor inhibition rates were significant between other groups and the control group and MMC group (P<0.05).The expression of P-gp and MGr1-Ag was highest in the control group and MMC group,the difference of expression of P-gp and MGr1-Ag were significance between other groups and control group and MMC group (P<0.05).MMC combined high dose ROS group and MMC combined cyclosporineA( CSA) group were least,there was no significant difference between them( P>0.05) .Conclu-sion Rosiglitazone inhibits the growth of SGC7901/VCR cell and decreases the expression of P-gp and MGr1-Ag,Rosiglitazone reverses drug resistance of nude mice xenografts of human gastric cancer SGC7901/VCR cells partly on MMC.%目的：探讨 PPARγ激动剂罗格列酮（ ROS ）逆转人胃癌 SGC7901／VCR 细胞裸鼠移植瘤对丝裂霉素（ MMC）的耐药作用及其可能机制。方法建立人胃癌SGC7901／VCR细胞裸鼠移植瘤模型，将48只裸鼠随机分为6组：空白对照组（生理盐水0．2 ml）、MMC组（ MMC 2．5 mg／kg）、ROS组（ ROS 100 mg／kg）、MMC＋ROS中剂量组（ MMC 2．5 mg／kg＋ROS 50 mg／kg）、MMC＋ROS高剂量组（MMC 2．5 mg／kg＋ROS 100 mg／kg）、MMC＋CSA组（MMC 2．5 mg／kg＋CSA 50 mg／kg）。每组8只裸鼠；用药40天后，观察各组裸鼠体重和移植瘤体积变化，计算抑瘤率，绘制移植瘤的生长曲线；Western-blot法检测P-gp和MGr1-Ag蛋白的表达。结果空白对照组、MMC组移植瘤瘤体积和抑瘤率差异无显著性，ROS组、MMC＋ROS中剂量组、MMC＋ROS高剂量组组、MMC＋CSA组与空白对照组、MMC组比较，移植瘤瘤体积和抑瘤率差异有显著性。空白对照组、MMC组中P-gp、MGr1-Ag蛋白表达最强，ROS组、MMC＋ROS中剂量组、MMC＋ROS大剂量组、MMC＋CSA组与空白对照组和MMC组P-gp、MGr1-Ag蛋白表达比较有统计学意义（ P＜0．05），MMC＋ROS大剂量组、MMC＋CSA组中其表达最弱，组间差异无统计学意义（P＞0．05）。结论罗格列酮可抑制人胃癌SGC7901／VCR细胞祼鼠移植瘤瘤体生长，罗格列酮可下调人胃癌SGC7901／VCR细胞裸鼠移植瘤组织中P-gp和MGr1-Ag蛋白的表达。罗格列酮可部分逆转人胃癌SGC7901／VCR细胞祼鼠移植瘤对丝裂霉素的耐药性。