二甲双胍联合奥沙利铂对肺癌裸鼠移植瘤 VEGF-C、VEGFR-3、CD44v6 和 β-catenin 表达的影响.

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 and β-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 and β-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 oxaliplatin-treated 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 andβ-catenin mRNA within four groups were 78.897, 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 en-hance the anti-tumor efficacy. [ABSTRACT FROM AUTHOR]