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Adenoviral‐mediated gene transfer of Gadd45a results in suppression by inducing apoptosis and cell cycle arrest in pancreatic cancer cell
Author(s) -
Li Yunfeng,
Qian Haili,
Li Xiao,
Wang Haijuan,
Yu Jing,
Liu Yongjun,
Zhang Xueyan,
Liang Xiao,
Fu Ming,
Zhan Qimin,
Lin Chen
Publication year - 2009
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1270
Subject(s) - cancer research , cell cycle , pancreatic cancer , cisplatin , cell cycle checkpoint , cancer , biology , apoptosis , cancer cell , medicine , chemotherapy , genetics
Background The extremely poor prognosis of patients with pancreatic ductal adenocarcinoma 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. Methods We evaluated the biological activity of Gadd45a in pancreatic ductal adenocarcinoma cancer‐derived cell lines and assessed the efficacy of a combined treatment with adenoviral‐mediated expression of Gadd45a (Ad‐G45a) and anticancer drug (Etoposide, cisplatin, 5‐fluorouracil, respectively) for the PANC1 cell line. Results 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. Gadd45a significantly increased the chemosensitivity of PANC1, which may be due to 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 status, indicating a higher chemosensitivity to cancer chemotherapy. Conclusions Gadd45a may be a promising candidate for use in cancer gene therapy in combination with chemotherapeutic agents. Copyright © 2008 John Wiley & Sons, Ltd.