Title: Rosiglitazone enhanced growth inhibition of transplanted lung adenocarcinoma by Cisplatin in nude mice
Abstract: Objective To investigate the synergistic effects of Rosiglitazone with Cisplatin on the growth of lung adenocarcinoma cell line A549 xenografted to nude mice.Methods A549 cells were transplanted into nude mice,and twenty-eight xenografts were established successively.They were then randomly divided into 7 groups:A(control group),B(Cisplatin 1 mg/kg),C(Cisplatin 4 mg/kg),D(Rosiglitazone 10 mg/kg),E(Rosiglitazone 30 mg/kg),F(Cisplatin 1 mg/kg + Rosiglitazone 10 mg/kg),G(Cisplatin 1 mg/kg + Rosiglitazone 30 mg/kg).Seven days after implantation,different treatments were served from the 4th day,and all mice were sacrificed after 29 days.The volumes of the transplanted tumors were measured every 4 days during the therapy.The tumor growth inhibiting rates of each group were calculated.Moreover,the curves of tumor growth were drawn.Subcutaneous tumor PPARγ,Bcl-2 and NFκB were determined by immunohistochemical method with image analysis system.Results In each treatment group,tumor growth was suppressed significantly by intraperitoneal injection of Cisplatin,Rosiglitazone and their combination resulted in a significant inhibition on the growth of A549 cells in vivo(P0.01),the combination group(Cisplatin 1 mg/kg + Rosiglitazone 30 mg/kg) showed synergic effect on inhibiting the growth of the xenografts with a q value of 1.29.Contrary to control group,the expression of subcutaneous tumor Bcl-2 and NFκB was obviously down-regulated and the PPARγwas up-regulated by Rosiglitazone and its combination with Cisplatin(P 0.001).Conclusion The ligand of PPARγ Rosiglitazone enhances the inhibition of proliferation and induction of apoptosis by treatment with Cisplation in lung adenocarcinoma cells in nude mice in vivo.Activation of PPARγ protein and down-regulation of Bcl-2 and NFκB possibly play important roles in chemosensitizng mechanism of Rosiglitazone in vivo.
Publication Year: 2008
Publication Date: 2008-01-01
Language: en
Type: article
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