The Expression Of VEGF, VEGF-C And PPARγ On The Gastric Carcinoma And Mechanism Of Proliferator-induced Angiogenesis-inhibited And Lymph Node Metastasis-inhibited By Rosiglitazone For Gastric Carcinoma Cell

Objective To investigate the significance of expression of peroxisome proliferator-activated receptor gamma(PPARγ), VEGF and VEGF-C in gastric carcinoma and their correlation. To determine whether PPARγcould affect clinicopathological characteristics of tumors. To report expression of PPARγ, VEGF and VEGF-C in human gastric cancer cell line MKN-45 and MKN-28 and the effection of PPARy ligand , Rosiglitazone, on proliferation of gastric carcinoma cell line. PPARγactivation could induce apoptosis of MKN-45 cells and MKN-28 and inhibit angiogenesis and lymph node metastasis of gastric carcinoma though changing VEGF and VEGF-C gene expression.Methods Immunohistochemical methods were adopted to examine the expression of PPARγ, VEGF and VEGF-C in 40 patients with gastric carcinoma; Thirty-six pairs of normal mucosa and cancer specimens were obtained from patients who had undergone gastrectomy for primary gastric cancernoma and subjected to reverse transcripatase-ploymerase chain reaction(RT-PCR) for PPARγ, VEGF and VEGF-C. PPARγ, VEGF and VEGF-C mRNA were examined by RT-PCR in MKN-45 cells and MKN-28 cells respectively. Proliferation was examined by MTT assay; Apoptosis and cell cycle distribution were examined by flow cytometry; Down regulation of VEGF and VEGF-C mRNA gene expression in MKN-45 cells after treatment with Rosiglitazone by real time PCR; Reduction of VEGF protein expression were examined in MKN-45 cells after treatment with Rosiglitazone by western blot.Results The positive rate of PPARγprotein was significantly higher in gastric carcinoma72.5%(40 cases)than in their paired adjacent mucosa 25%(40 cases) and normal mucosal7.5%(40 cases); PPARγespression was well correlated with VEGF(r=0.388, p=0.013; t=3.24, p=0.003) and VEGF-C (r=0.441, p=0.004; t=2.624, p=0.014) in protein and mRNA leves; Rosiglitazone showed dose-related and time-related inhibitory effects on the proliferation of the gastric cancer cells by MTT; Apoptosis was reduced and cell cycle was arrested in G1-phase after treated with rosiglitazone by FCM; PPARγ, VEGF and VEGF-C mRNA was expressed in MKN-45 cells and MKN-28 cells though RT-PCR; Dose-related inhibitory effects of VEGF and VEGF-C gene expression in MKN-45 cells by real time PCR after treatment with compared with PPARγagonist (rosiglitazone); VEGF protein expression was effected in MKN-45 cells by western blot using rosiglitazone for 48 hours.Conclusion :The results suggest that there are a closely relationship in PPARγand VEGF ,VEGF-C. Rosiglitazone could induce apoptosis of human gastric cancer cell MKN-45 and MKN-28 and decrease expression of VEGF ,VEGF-C gene. Thereby rosiglitazone may inhibit the growth , metastasis and infiltration of tumor, which may be an useful therapeutic agent in the treatment of gastric carcinoma.