Experimental Study of Chemosensitization of Rosiglitazone on Primary Subcutaneous Xenograft of Lung Adenocarcinoma in Nude Mice

Objective To investigate the effects of chemosensitization of rosiglitazone( ROZ) on primary subcutaneous xenograft of lung adenocarcinoma in nude mice and its mechanism. Methods Human lung adenocarcinoma A549 cells was established in xenograft nude mice. 28 female Balb /c-nu mice with lung adenocarcinoma were randomly divided into 7 groups. ①control group; ② low-dose cisplatin( DDP) group( 1 mg /kg); ③ high-dose DDP group( 4 mg /kg); ④ low-dose ROZ group( 10 mg /kg); ⑤ high-dose ROZ group( 30 mg /kg); ⑥ low-dose DDP( 1 mg /kg) plus low-dose ROZ group( 10 mg /kg); ⑦ low-dose DDP( 1 mg /kg) plus high-dose ROZ group( 30 mg /kg); all the mice received intraperitoneal injection every other day for 8times. And they were sacrificed 48h after the last injection. Subcutaneous tumor were subjected to histological examination. Morphological changes were observed by HE staining. Expression of PPARγ,bcl-2 and caspase-3 were detected by immunohistochemistry. Results In all treatment groups,tumor growth was suppressed significantly. Tumor weight was significantly lower than that of the control group( P 0. 01),and tumor volume was significantly smaller than that of the control group( P 0. 01). The antitumor effect of DDP plus ROZ was significantly enhanced compared with low-dose DDP( P 0. 05),The inhibition rates were52. 11% and 83. 80%,respectively. Expression of PPARγ and caspase-3 increased in all ROZ-treatment groups,and expression of bcl-2 decreased in all ROZ-treatment groups. The difference was statistically significant( P 0. 05). This difference significantly increased between the combined treatment group and the control group( P 0. 01). Conclusion Rosiglitazone has chemosensitizing effect on human lung adenocarcinoma xenografts in nude mice,and its mechanism maybe associated with increasing expression of PPARγ and caspase-3,and decreasing expression of bcl-2.