Effect and mechanism of Mitomycin C combined with recombinant adeno-associated virus type II against glioma.
Effect and mechanism of Mitomycin C combined with recombinant adeno-associated virus type II against glioma.
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DOI：
10.3390/ijms15010001
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发表时间：
2013-12-19
影响因子：
5.6
通讯作者：
Deng Y
中科院分区：
文献类型：
--
作者：
Ma H;Zhang Y;Wang H;Han C;Lei R;Zhang L;Yang Z;Rao L;Qing H;Xiang J;Deng Y
探讨化疗药物丝裂霉素C（MMC）联合重组腺相关病毒II（rAAV 2）治疗癌症的效果，并研究MMC影响rAAV 2生物活性的机制。通过检测GFP和TNF在人脑胶质瘤细胞系中的表达水平来评价MMC的联合作用，并通过AAV转导相关信号分子来研究MMC对rAAV介导的基因表达的影响机制。将rAAV-EGFP或rAAV-TNF单独或与MMC混合注射C57和BALB/c裸鼠，观察MMC对AAV介导的基因表达和肿瘤抑制的影响。MMC在体外和体内均显示出提高rAAV 2的感染活性。增强被认为是独立的初始rAAV 2受体结合阶段或随后的第二链合成的靶DNA，但与细胞周期阻滞，随后被阻断的基因组降解。将MMC与rAAV 2组合体内注射到动物的肿瘤中导致肿瘤生长的显著抑制。首次证明MMC可增强rAAV 2介导的目的基因的表达水平。rAAV 2与MMC的联合应用有望成为肿瘤治疗的新策略。
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.
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影响因子：
82.9
作者：
Qing, K;Mah, C;Srivastava, A
通讯作者：
Srivastava, A
影响因子：
5.4
作者：
Ferrari, FK;Samulski, T;Samulski, RJ
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影响因子：
25.7
作者：
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
4.2
作者：
Bartlett, JS;Samulski, RJ;McCown, TJ
通讯作者：
McCown, TJ