Effect Of Overexpression Of Gadd45a On Biological Behavior Of Pancreatic Cancer Cell

The extremely poor prognosis of patients with pancreatic ductal adenocarcinoma(PDAC) indicates the need for novel therapeutic approaches. The growth arrest and DNA damage-inducible(Gadd) gene Gadd45a is a member of a group of genes that are induced by DNA damaging agents and growth arrest signals.In this report,we have analyzed the biological activity of Gadd45a upon pancreatic ductal adenocarcinoma cancer-derived cell lines.We report that Gadd45a is variously expressed in cell lines derived from pancreatic ductal adenocarcinoma cancer and adenoviral-mediated expression of Gadd45a (Ad-G45a) in these cells results in apoptosis via caspase activation and cell-cycle arrest in the G2/M phase.Furthermore,we assessed the efficacy of a combined treatment with Ad-G45a and anticancer drugs(Etoposide,cisplatin, 5-fluorouracil,respectively) for PANC1 cell line and found that Gadd45a significantly increased the chemosensitivity of PANC1 to chemotherapeutic agents,which may be resulted from abundant apoptosis induction and cell cycle arrest.By combinational treatment of Ad-G45a infection and chemotherapeutics, Gadd45a expression was elevated to a higher extent in cancer cells with wild-type p53 than in that with knocked-out p53,indicating a higher chemosensitivity to cancer chemotherapy.In PANC1 xenograft models, Ad-G45a significantly inhibited the growth of tumor(74.8%).Collectively,our results suggest that Gadd45a may paly nagative roles in cancer cell growth and may be a promising molecule used for the cancer gene therapy in combination with chemotherapeutic agents.