Adenoviral-mediated gene transfer of Gadd45a results in suppression by inducing apoptosis and cell cycle arrest in pancreatic cancer cell.
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.
Li
Yunfeng
Y
State Key Laboratory of Molecular Oncology, Cancer Institute/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Qian
Haili
H
Li
Xiao
X
Wang
Haijuan
H
Yu
Jing
J
Liu
Yongjun
Y
Zhang
Xueyan
X
Liang
Xiao
X
Fu
Ming
M
Zhan
Qimin
Q
Lin
Chen
C
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D002945:Cisplatin; D005047:Etoposide; D005472:Fluorouracil; D047908:Intracellular Signaling Peptides and Proteins; D000097642:GADD45 Proteins