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World J Gastroenterol. Oct 28, 2008; 14(40): 6254-6260
Published online Oct 28, 2008. doi: 10.3748/wjg.14.6254
Inhibition of pancreatic carcinoma cell growth in vitro by DPC4 gene transfection
Wei Shen, Guo-Qing Tao, De-Chun Li, Xing-Guo Zhu, Xia Bai, Bing Cai
Wei Shen, Guo-Qing Tao, Bing Cai, Department of General Surgery, Wuxi People’s Hospital, Wuxi 214023, Jiangsu Province, China
De-Chun Li, Xing-Guo Zhu, General surgery department of the first affiliated hospital to Suzhou University, Suzhou 215007, Jiangsu Province, China
Xia Bai, Jiangsu Institute of Hematology, first affiliated hospital to Suzhou University, Suzhou, 215007, Jiangsu Province, China
Author contributions: Shen W, Tao GQ, Li DC and Cai B designed research; Shen W, Zhu XG, Bai X performed research; Cai B contributed with the EM; Shen W wrote the paper.
Correspondence to: Wei Shen, Department of General Surgery, Wuxi People’s Hospital, Wuxi 214023, Jiangsu Province, China. shenweico@163.com
Telephone: +86-510-82700778 Fax: +86-510-85350555
Received: May 3, 2008
Revised: July 14, 2008
Accepted: July 21, 2008
Published online: October 28, 2008
Abstract

AIM: To detect the expression of DPC4 in malignant and non-malignant specimens of human pancreas, and observe the inhibition of retroviral pLXSN containing DPC4 on pancreatic carcinoma cells in vitro.

METHODS: The expression of DPC4 was determined in 40 pancreatic adenocarcinoma and 36 non-malignant pancreatic specimens by reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohisto-chemistry. Furthermore, we constructed retroviral vectors containing DPC4, which then infected the pancreatic carcinoma cell line BxPC-3. Cell growth in vitro after being infected was observed, and the vascular endothelial growth factor (VEGF) mRNA level in the daughter cells was determined by semi-quantitative PCR assay.

RESULTS: The RT-PCR assay showed a positive rate of DPC4 mRNA in 100% (36/36) of normal specimens, compared to 40% (16/40) in adenocarcinoma specimens. The regional and intense positive cases of DPC4 expression in adenocarcinoma detected by immunohistochemistry were 10 and four, whereas it was all positive expression in normal tissues. There was a significant difference of DPC4 expression between them. The stable expression of DPC4 in the pancreatic carcinoma cells BxPC-3 could be resumed by retroviral vector pLXSN transfection, and could inhibit cell growth in vitro. Rather, DPC4 could decrease VEGF mRNA transcription levels.

CONCLUSION: The deletion of DPC4 expression in pancreatic carcinoma suggests that loss of DPC4 may be involved in the development of pancreatic carcinoma. The retroviral vector pLXSN containing DPC4 can inhibit the proliferation of pancreatic carcinoma cells, and down-regulate the level of VEGF.

Keywords: Gene therapy; Pancreatic carcinoma; Retroviral vector