Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24
Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24
复制标题
顺铂与携带 MDA-7/IL-24 的溶瘤腺病毒联合增强肿瘤细胞死亡
DOI：
10.1038/aps.2009.16
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发表时间：
2009-04-01
影响因子：
8.2
通讯作者：
Wang, Yi-gang
中科院分区：
文献类型：
--
作者：
Wu, Yu-mei;Zhang, Kang-jian;Wang, Yi-gang
Aim:The aim of this study was to creatively implement a novel chemo-gene-virotherapeutic strategy and further strengthen the antitumor effect in cancer cells by the combined use of ZD55-IL-24 and cisplatin.Methods:ZD55-IL-24 is an oncolytic adenovirus that harbors interleukin 24 (IL-24), which has a strong antitumor effect and was identified and evaluated by PCR, RT-PCR, and Western blot analysis. Enhancement of cancer cell death using a combination of ZD55-IL-24 and cisplatin was assessed in several cancer cell lines by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cytopathic effect (CPE) assay. Apoptosis induction by treatment with ZD55-IL-24 and/or cisplatin was detected in BEL7404 and SMMC7721 by morphological evaluation, apoptotic cell staining, and flow cytometry analysis. In addition, negative effects on normal cells were evaluated in the L-02 cell line using the MTT assay, the CPE assay, morphological evaluation, apoptotic cell staining, and flow cytometry analysis.Results:The combination of ZD55-IL-24 and cisplatin, which is superior to ZD55-IL-24, cisplatin, and ZD55-EGFP, as well as ZD55-EGFP plus cisplatin, resulted in a significantly increased effect. Most importantly, conjugation of ZD55-IL-24 with cisplatin had toxic effects equal to that of cisplatin and did not have overlapping toxicities in normal cells.Conclusion:This study showed that ZD55-IL-24 conjugated with cisplatin exhibited a remarkably increased cytotoxic and apoptosis-inducing effect in cancer cells and significantly reduced the toxicity in normal cells through the use of a reduced dose.
