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Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma
School of Life Science, Beijing Institute of Technology, Haidian District, Beijing 100081, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 29 July 2013; in revised form: 9 December 2013 / Accepted: 9 December 2013 / Published: 19 December 2013
Abstract: The effect of chemotherapy drug Mitomycin C (MMC) in combination with recombinant adeno-associated virus II (rAAV2) in cancer therapy was investigated, and the mechanism of MMC affecting rAAV2’s bioactivity was also studied. The combination effect was evaluated by the level of GFP and TNF expression in a human glioma cell line, and the mechanism of MMC effects on rAAV mediated gene expression was investigated by AAV transduction related signal molecules. C57 and BALB/c nude mice were injected with rAAV-EGFP or rAAV-TNF alone, or mixed with MMC, to evaluate the effect of MMC on AAV-mediated gene expression and tumor suppression. MMC was shown to improve the infection activity of rAAV2 both in vitro and in vivo. Enhancement was found to be independent of initial rAAV2 receptor binding stage or subsequent second-strand synthesis of target DNA, but was related to cell cycle retardation followed by blocked genome degradation. In vivo injection of MMC combined with rAAV2 into the tumors of the animals resulted in significant suppression of tumor growth. It was thus demonstrated for the first time that MMC could enhance the expression level of the target gene mediated by rAAV2. The combination of rAAV2 and MMC may be a promising strategy in cancer therapy.
Keywords: recombinant adeno-associated virus II; mitomycin C; glioma
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Ma, H.; Zhang, Y.; Wang, H.; Han, C.; Lei, R.; Zhang, L.; Yang, Z.; Rao, L.; Qing, H.; Xiang, J.; Deng, Y. Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma. Int. J. Mol. Sci. 2014, 15, 1-14.
Ma H, Zhang Y, Wang H, Han C, Lei R, Zhang L, Yang Z, Rao L, Qing H, Xiang J, Deng Y. Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma. International Journal of Molecular Sciences. 2014; 15(1):1-14.
Ma, Hong; Zhang, Yunjia; Wang, Hailong; Han, Chuanhui; Lei, Runhong; Zhang, Lei; Yang, Zuye; Rao, Ling; Qing, Hong; Xiang, Jim; Deng, Yulin. 2014. "Effect and Mechanism of Mitomycin C Combined with Recombinant Adeno-Associated Virus Type II against Glioma." Int. J. Mol. Sci. 15, no. 1: 1-14.