The Study On The Radiosensitivity Effect And Mechanism Of PPARγ Agonist Rosiglitazone On Pancreatic Cancer Cells

Objective To study the expression of peroxisome proliferator-activated receptor gama (PPARγ) in pancreatic cancer tissues and tumor-adjacent normal pancreatic tissues and to investigate the effects and mechanisms of PPARγ agonist rosiglitazone on pancreatic cancer cell lines Panc1 and Patu8988 treated with X-ray.Methods (1) 18 pairs of paraffin sections of pancreatic cancer tissues and corresponding tumor-adjacent normal pancreatic tissues were collected for immunohistochemistry assay to detecte the expression of PPARγ. (2) MTT assay was used to screen drug concentration and to test the viability of Panc1 and Patu8988 cells treated with rosiglitazone and/or IR. (3) Scratch migration assay was used to detect the migration ability of the cells. (4) The invasion ability was detected by transwell assay. (5) Clonogenic data was obtained to evaluate the effects on the regulation of radiosensitivity. (6) Immunofluorescence and Western blot assays were used to detect the expression level of PPARγ in nuclei treated with rosiglitazone. (7) Microarray was used to investigate changes of genes involved.Results The expression of PPARγ of cancer tissues was much higher compared to para-carcinoma tissues. The sections were scored and the scores of cancer tissues were significantly higher than the normal ones (P< 0.01). With the increasing concentrations of rosiglitazone, the viability of Panc1 and Patu8988 cells decreased. Pretreated for 48 hours, rosiglitazone in combination with X-rays significantly reduced the proliferation and invasion of Panc1 and Patu8988 cells. Immunofluorescence and Western-blot experiments showed that rosiglitazone can increase the expression of PPARγ in nuclei. Microarray data showed that the activation of PPARγ would modulate hundreds of genes, including FABP4 and Zip7.Conclusion The expression of PPARy of pancreatic cancer is higher than the normal ones in the cytoplasms. And the increased raidosensitivity may be contributed to the expression modulation of many signal pathways related to radiotherapy efficacy, mediated by FABP4, Zip7, etc.