A promising cancer gene therapy agent based on the matrix protein of vesicular stomatitis virus.

Zhao JM; Wen YJ; Li QWang YSWu HBXu JRChen XCWu YFan LYYang HSLiu TDing ZYDu XBDiao PLi JWu HBKan BLei SDeng HXMao YQZhao XWei YQ

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A promising cancer gene therapy agent based on the matrix protein of vesicular stomatitis virus.

机译：A promising cancer gene therapy agent based on the matrix protein of vesicular stomatitis virus.

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The matrix (M) protein of vesicular stomatitis virus (VSV) plays a key role in inducing cell apoptosis during infection. To investigate whether M protein-mediated apoptosis could be used in cancer therapy, its cDNA was amplified and cloned into eukaryotic expression vector pcDNA3.1(+). The recombinant plasmid or the control empty plasmid pcDNA3.1(+) was mixed with cationic liposome and introduced into various tumor cell lines in vitro, including lung cancer cell LLC, A549, colon cancer cell CT26 and fibrosarcoma cell MethA. Our data showed that the M protein induced remarkable apoptosis of cancer cells in vitro compared with controls. Fifty micrograms of plasmid in a complex with 250 microg cationic liposome was injected intratumorally into mice bearing LLC or MethA tumor model every 3 days for 6 times. It was found that the tumors treated with M protein plasmid grew much more slowly, and the survival of the mice was significantly prolonged compared with the mice treated with the control plasmid. In MethA fibrosarcoma, the tumors treated with M protein plasmid were even completely regressed, and the mice acquired longtime protection against the same tumor cell in rechallenge experiments. Both apoptotic cells and CD8(+) T cells were widely distributed in M protein plasmid-treated tumor tissue. Activated cytotoxic T lymphocytes (CTLs) were further detected by means of (51)Cr release assay in the spleen of the treated mice. These results showed that M protein of VSV can act as both apoptosis inducer and immune response initiator, which may account for its extraordinary antitumor effect and warrant its further development in cancer gene therapy.

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来源
《The FASEB Journal》 |2008年第12期|4272-4280|共9页
作者
Zhao JM; Wen YJ; Li QWang YSWu HBXu JRChen XCWu YFan LYYang HSLiu TDing ZYDu XBDiao PLi JWu HBKan BLei SDeng HXMao YQZhao XWei YQ;
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State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.;

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原文格式 PDF
正文语种英语
中图分类生物化学;
关键词
Plasmids; M Protein; multiple myeloma; Laboratory mice; Cells; 质粒; 细胞;

A promising cancer gene therapy agent based on the matrix protein of vesicular stomatitis virus.

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