【摘要】 目的探讨二甲双胍联合奥沙利铂对肺癌裸鼠移植瘤血管内皮生长因子-C(VEGF-C)、血管内皮生长因子受体-3(VEGFR-3)、CD44变异体蛋白6(CD44v6)和β-链蛋白(β-catenin)分子表达水平的影响。方法建立肺癌裸鼠移植瘤模型,将裸鼠随机分为二甲双胍组、奥沙利铂组、联合用药组及对照组,每组分别给予二甲双胍、奥沙利铂、二甲双胍+奥沙利铂及灭菌蒸馏水等干预,42 d后处死动物,留取肿瘤组织,分别采用免疫组织化学法及实时荧光定量PCR法检测肿瘤组织中VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白及mRNA的表达。结果二甲双胍组、奥沙利铂组和联合用药组的抑瘤率分别为28.97%、34.37%和50.27%。与对照组相比,奥沙利铂组、联合用药组VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白及mRNA表达水平均降低(P均<0.05);与二甲双胍组、奥沙利铂组比较,联合用药组VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白及mRNA表达水平均降低(P均<0.05),VEGF-C、VEGFR-3、CD44v6和β-catenin蛋白组间比较有统计学差异(F值分别为79.281、151.275、171.294、164.149,P均<0.01);VEGF-C、VEGFR-3、CD44v6和β-catenin mRNA组间比较差异均有统计学意义(F值分别为78.897、81.029、64.100、83.892,P均<0.01)。结论奥沙利铂及二甲双胍均可抑制VEGF-C、VEGFR-3、CD44v6和β-catenin的表达,联合应用抑制效果更强。更多还原

【Abstract】 Objective To investigate the effects of metformin combined with oxaliplatin on the expression levels of vascular endothelial growth factor-C( VEGF-C),vascular endothelial growth factor receptor-3( VEGFR-3),CD44v6 andβ-catenin of lung cancer xenograft in nude mice. Methods We established human lung cancer xenograft models in the nude mice. The nude mice were randomly divided into metformin-treated,oxaliplatin-treated,metformin combined with oxaliplatin-treated and untreated control groups. Forty-two days after administration,all the nude mice were sacrificed and tumor tissues were sampled. The protein and mRNA expression of VEGF-C,VEGFR-3,CD44v6 and β-catenin in the tumor tissues was detected by immumohistochemical method and florescent real-time quantitative PCR,repectively. Results The respective tumor inhibition rates of metformin-treated group,oxaliplatin-treated group and metformin combined with oxaliplatin-treated group were 28. 97%,34. 37% and 50. 27%. The expression levels of VEGF-C,VEGFR-3,CD44v6 andβ-catenin protein and mRNA in the oxaliplatin-treated and metformin combined with oxaliplatin-treated groups were lower than those in the control group,respectively( all P < 0. 05). Compared with the metformin-treated group and oxaliplatintreated group,the expression levels of VEGF-C,VEGFR-3,CD44v6 and β-catenin protein and mRNA of the metformin combined with oxaliplatin-treated group were lower,respectively( all P < 0. 05). F values about comparison of VEGF-C,VEGFR-3,CD44v6 and β-catenin proteins within four groups were 79. 281,151. 275,171. 294 and 164. 149,respectively( all P < 0. 01); F values about comparison of VEGF-C,VEGFR-3,CD44v6 and β-catenin mRNA within four groups were78. 897,81. 029,64. 100 and 83. 892,respectively( all P < 0. 01). Conclusions Using oxaliplatin or metformin can inhibit the expression of VEGF-C,VEGFR-3,CD44v6 and β-catenin. The combination of metformin and oxaliplatin can enhance the anti-tumor efficacy.更多还原