Rosiglitazone Enhanced Growth Inhibition Of Cisplatin On A549 Cell Line Xenogragft In Nude Mice By Activating PPARγ

Objective:To observe the synergistic effects of Rosiglitazone and Cisplatin on the growth of lung adenocarcinoma A549 xenogragft in nude mice, and to investigate the mechanism of the therapeutic and synergistic action whether is involved in activating PPARγ.Methods:Human lung carcinomal cell line (A549) cells were cultured in vitro, then A549 cells were transplanted in nude mice. Twenty-eight xenogragfts in nude mice were established successively. They were then randomly divided into seven groups. A(N.S group),B(Cisplatin 1mg/kg),C(Cisplatin 4mg/kg),D(Rosiglitazone 10mg/kg), E(Rosiglitazon30mg/kg),F(Rosiglitazon10mg/kg+Cisplatin1mg/kg),G(Rosiglitazone30mg/kg+Cisplatin1mg/kg).Seven days after implantation, different treatments were served. The volumes of the xenogragfts were measured respectively during the therapy time. The tumor growth inhibiting rates of each group were calculated. Moreover, the curves of tumor growth were drew. Xenogragft was subjected to histological examination. Subcutaneous xenogragft PPARγ, Bcl-2 and NFκB were determined by immunohistochemistry method.Results: Therapeutic trial of human lung carcinoma xenografts in nude mouse model indicated that In each treatment group, tumor growth was suppressed significantly, intraperitoneal injection of Cisplatin, Rosiglitazon and their combination resulted in a significant inhibition on the growth of human lung carcinoma xenografts A549 in vivo(P<0.01), The tumor weight inhibitory rate of DDP at 1mg/kg, 4mg/kg was 30.28%, 65.85%,respectively. The tumor weight inhibitory rate of ROZ at 10mg/kg, 30mg/kg was 38.38%, 49.65% respectively. The tumor weight inhibitory rate of combination groups was 52.11%, 83.80%. The effect of inhibiting tumor growth was significantly strengthened. The combination group (Rosiglitazone 30mg/kg+ Cisplatin 1mg/kg) showed synergia effect on inhibiting the growth of the xenografts with a q value of 1.29. Campare to control group, Bcl-2 and NFκB expression of subcutaneous xenografts was obviously down-regulated and the PPARγwas up-regulated by Rosiglitazone (P<0.05) and the combined group(P<0.001).Conclusion:1) Rosiglitazone can inhibit the growth of human lung carcinoma xenograft in nude mice.2) Rosiglitazone combined with Cisplatin can significantly inhibit the growth of human lung carcinoma xenograft in nude mice in dose-dependent manner.3) The inhibition of growth by Rosiglitazone combined with Cisplatin are associated with up-regulation of PPARγprotein level expression and down-regulation of NFκB,Bcl-2protein level expression.