Dichloroacetate (DCA) enhances tumor cell death in combination with oncolytic adenovirus armed with MDA-7/IL-24
Dichloroacetate (DCA) enhances tumor cell death in combination with oncolytic adenovirus armed with MDA-7/IL-24
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二氯乙酸 (DCA) 与携带 MDA-7/IL-24 的溶瘤腺病毒结合可增强肿瘤细胞死亡
DOI：
10.1007/s11010-010-0397-6
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发表时间：
2010-02
影响因子：
4.3
通讯作者：
Xie, Guoliang
中科院分区：
文献类型：
--
作者：
Niu, Na;Xiao, Lianli;Wang, Yigang;Qian, Jing;Li, Xin;Xie, Guoliang
二氯乙酸（DCA）是一种代谢调节剂，用于治疗乳酸酸中毒和遗传性线粒体疾病。最近的一项研究表明，DCA可以通过线粒体凋亡途径诱导多种肿瘤细胞凋亡，而不影响正常细胞。ONYX-015 （dl 1520）是一种通过缺失5型腺病毒DNA的E1B-55kD基因而获得的溶瘤腺病毒，它在肿瘤细胞中进行了高效和选择性的复制。ZD55-IL-24是一种E1B-55kD缺失的携带白介素-24 （IL-24，也称为黑色素瘤分化相关基因-7）的溶瘤腺病毒，在多种肿瘤细胞中显示出强大的抗肿瘤功效，对正常细胞无明显毒性。鉴于DCA与ZD55-IL-24或ONYX-015联合使用具有良好的治疗效果和较低的毒性，我们在体外实验中考察了DCA与ZD55-IL-24或ONYX-015联合使用是否具有更有效的抗肿瘤活性。因此，我们使用MTT法测试了联合治疗对正常肝细胞L-02和QSG-7701的细胞毒性。我们的研究结果表明，DCA与ONYX-015或ZD55-IL-24联合治疗比单独使用DCA或病毒具有更强的抗肿瘤活性，并且在正常细胞中没有叠加毒性。因此，提出了一种将溶瘤腺病毒与毒性相对较低且无严重副作用的药物联合治疗的新方法。
Dichloroacetate (DCA) is a metabolic modulator for the treatment of lactic acidosis and inherited mitochondrial diseases. A recent study showed that DCA treatment could induce apoptosis in many kinds of tumor cell lines via mitochondrial apoptotic pathway while sparing normal cells. ONYX-015 (dl 1520) is one of the oncolytic adenoviruses developed by the deletion of E1B-55kD gene of type 5 adenoviral DNA, and it replicates efficiently and selectively in tumor cells. ZD55-IL-24, an E1B-55kD deleted oncolytic adenovirus carrying interleukin-24 (IL-24, also called melanoma differentiation associated gene-7), had showed potent antitumor efficacy in a variety of tumor cells and exerted no apparent toxicity on normal cells. Given both the good therapeutic effect and low toxicity of these agents, here we investigated whether DCA in combination with ZD55-IL-24 or ONYX-015 could have more efficient antitumor activity in vitro experiments. Therefore, we tested the cytotoxicity of combination therapy in normal hepatic cells L-02 and QSG-7701 using the MTT assay. Our results showed that DCA combined with ONYX-015 or ZD55-IL-24 exhibited more potent antitumor activity than DCA or virus alone, and the combination treatment did not have superimposed toxicities in normal cells. Thus, a novel combination therapy associating oncolytic adenoviruses with relatively low toxic drug without severe side effects was proposed.
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影响因子：
8.8
作者：
Michelakis, E. D.;Webster, L.;Mackey, J. R.
通讯作者：
Mackey, J. R.
DOI：
10.1016/s1532-0456(03)00082-6
发表时间：
2003-06-01
影响因子：
3.9
作者：
Hassoun, EA;Ray, S
通讯作者：
Ray, S
DOI：
10.1073/pnas.0804089105
发表时间：
2008-07-15
影响因子：
11.1
作者：
Sauane, Moira;Su, Zao-Zhong;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
11.2
作者：
Sauane, Moira;Gupta, Pankaj;Fisher, Paul B.
通讯作者：
Fisher, Paul B.
影响因子：
6.4
作者：
Zhao, L.;Dong, A.;Liu, X.
通讯作者：
Liu, X.