Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL |
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Authors: | Qiuwei Pan Bisheng Liu Jin Liu Rong Cai Yigang Wang Cheng Qian |
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Institution: | (1) Xin Yuan Institute of Medicine and Biotechnology, Life Science College, Zhejiang Sci-Tech University, Hangzhou, 310018, China |
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Abstract: | Chemoresistance and side effects are considered as the major obstacles in cisplatin-based chemotherapy of various human malignant
tumors. Conjugation with cancer-specific apoptotic stimuli TRAIL or typical viro-agent ONYX-015 has been extensively investigated
to enhance the antitumor activity of cisplatin. In this study, we presented a novel chemo-gene-virotherapeutic strategy to
further improve the toxic effects in cancer cells and reduce the damage in normal cells. Here, an oncolytic adenoviral vector
(ZD55), with a deletion of E1B 55-kDa gene, was employed to express the therapeutic TRAIL gene by constructing a recombinant virus ZD55-TRAIL. Exogenous gene delivery
efficacy was determined by both in vitro and in vivo experiments and enhanced cytotoxicity of combined treatment of ZD55-TRAIL
with cisplatin was evaluated in several cancer cell lines. Moreover, negative effects on normal cells have been tested in
both L-02 and MRC-5 cell lines by MTT assay and apoptotic cell staining. According to our observation, combination of ZD55-TRAIL
with cisplatin exhibited an apparent synergistic cytotoxicity in cancer cells, yet significantly abolished the negative toxicity
in normal cells by reducing the dosage. Thus, a novel chemo-gene-virotherapeutic strategy for cancer therapy was proposed. |
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Keywords: | TRAIL Cisplatin Oncolytic adenovirus Cancer |
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