Brief Reports
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 1, 2004; 10(19): 2874-2877
Published online Oct 1, 2004. doi: 10.3748/wjg.v10.i19.2874
Human endostatin gene transfer, either naked or with liposome, has the same inhibitory effect on growth of mouse liver tumor cells in vivo
Chun-Hong Ma, Yan Zhang, Xiao-Yan Wang, Li-Fen Gao, Hua Liu, Chun Guo, Su-Xia Liu, Ying-Lin Cao, Li-Ning Zhang, Wen-Sheng Sun
Chun-Hong Ma, Yan Zhang, Xiao-Yan Wang, Li-Fen Gao, Hua Liu, Chun Guo, Su-Xia Liu, Ying-Lin Cao, Li-Ning Zhang, Wen-Sheng Sun, Institute of Immunology, Medical College of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the National Natural Science Foundation of China, No. 30100078 and Huo Yingdong Educational Fund, No.81035
Correspondence to: Dr. Chun-Hong Ma, Institute of Immunology, Medical College of Shandong University, Jinan 250012, Shandong Province, China. machunhong@sdu.edu.cn
Telephone: +86-531-8382038
Received: November 21, 2003
Revised: December 15, 2003
Accepted: December 22, 2003
Published online: October 1, 2004
Abstract

AIM: To explore a safe and efficient strategy of tumor therapy using anti-angiogenetic agents.

METHODS: Endostatin gene with a signal sequence of human IgG γ chain was amplified by PCR and cloned into pVAX1 plasmid which was the only vector authorized by FDA in clinical trial to construct a recombinant plasmid named as pVAX-sEN. The recombinant plasmid was detected with Eco I/Kpn I and DNA sequencing. BALB/c mice bearing hepatocarcinoma cell line H22 were treated with naked pVAX-sEN or liposome-DNA complex in which the dose of DNA and the ratio of DNA and liposome were different from each other. To compare the efficiency of gene transfection, expression of endostatin at the treated tumor site was assayed with ELISA. To investigate the effect of pVAX1-sEN on hepatocellular carcinoma, pVAX-sEN either naked or in liposome-DNA complex was injected into BALB/c mice bearing H22, then the diameter of tumors was measured, microvessel density was detected by immunohistochemistry, endostatin expression in vivo was assayed at different time points.

RESULTS: DNA sequencing showed the endostatin gene with the signal peptide was correctly cloned. In situ gene expression assay indicated that both the ratio of DNA and liposome and the dose of DNA could affect the gene transfection efficiency. Interestingly, naked pVAX-sEN had a similar in situ endostatin expression to pVAX-sEN with liposome. Animal experiments showed that pVAX-sEN together with pVAX-sEN-liposome complex could efficiently suppress the growth of mouse hepatoma cells.

CONCLUSION: Naked endostatin plasmid intratumoral injection can get a similar gene transfection efficiency to liposome-DNA complex when used in situ.

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