Cao GW, Qi ZT, Pan X, Zhang XQ, Miao XH, Feng Y, Lu XH, Shigeki K, Ping D. Gene therapy for human colorectal carcinoma using human CEA promoter controled bacterial ADP-ribosylating toxin genes: PEA and DTA gene transfer. World J Gastroenterol 1998; 4(5): 388-391 [PMID: 11819328 DOI: 10.3748/wjg.v4.i5.388]
Corresponding Author of This Article
Dr. Guang-Wen Cao, Department of Microbiology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China. guangwen@ecmu.org.cn
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Original Articles
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World J Gastroenterol. Oct 15, 1998; 4(5): 388-391 Published online Oct 15, 1998. doi: 10.3748/wjg.v4.i5.388
Gene therapy for human colorectal carcinoma using human CEA promoter controled bacterial ADP-ribosylating toxin genes: PEA and DTA gene transfer
Guang-Wen Cao, Zhong-Tian Qi, Xin Pan, Xiao-Qin Zhang, Xiao-Hui Miao, Yan Feng, Xin-Hua Lu, Kuriyama Shigeki, Du Ping
Guang-Wen Cao, Zhong-Tian Qi, Xin Pan, Xiao-Qin Zhang, Xiao-Hui Miao, Yan Feng, Xin-Hua Lu, Du Ping, Department of Microbiology, Second Military Medical University, Shanghai 200433, China
Kuriyama Shigeki, Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan
Guang-Wen Cao, male, born on 1965-09-22 in Benxi City, Liaoning Province, graduated from the Second Military Medical University as a postgraduate in 1992. Now Associate professor of microbiology, majoring the tissue-specific gene therapy for tumors of digestive system and HBV persistent infection, having 43 papers and 2 books published.
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, i- No.39770834.
Correspondence to: Dr. Guang-Wen Cao, Department of Microbiology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 200433, China. guangwen@ecmu.org.cn
Received: July 6, 1998 Revised: August 22, 1998 Accepted: September 26, 1998 Published online: October 15, 1998
Abstract
AIM: To establish a tissue-specific gene therapy for colorectal carcinoma using bacterial ADP-ribosylating toxin genes.
METHODS: Pseudomonas exotoxin A domain II +III (PEA) was cloned from genomic DNA of Pseudomonas aeruginosa. PEA and diphtheria toxin A chain gene (DTA) were modified to express eukaryotically. After sequencing, the toxin genes under the control of human carcinoembryonic antigen (CEA) promoter were cloned into retroviral vectors to construct CEAPEA and CEADTA respectively. In vitro cotransfection of the constructs with luciferase vectors and in vivo gene transfer in nude mice were subsequently carried out.
RESULTS: Both CEAPEA and CEADTA specifically inhibited the reporter gene expression in the CEA positive human colorectal carcinoma (CRC) cells in vitro. Direct injection of CEAPEA and CEADTA constructs into the established human tumors in BALB/c nude mice led to significant and selective reductions in CRC tumor size as compared with that in control groups.
CONCLUSION: The toxin genes, working as therapeutic genes, are suitable for the tissue-specific gene therapy for colorectal carcinoma.
