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Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL

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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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Acknowledgments

This work was supported by the 973 Project (No.2004CB518804), The 863 project (No. 20060102Z1107), Zhejiang Provincial Grant (No. 2006C23006), Zhejiang funds for the returned students (No. 116153A4I0538) and Zhejiang natural science funds (No. Y205282).

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Authors and Affiliations

  1. Xin Yuan Institute of Medicine and Biotechnology, Life Science College, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Qiuwei Pan, Bisheng Liu, Jin Liu, Rong Cai, Yigang Wang & Cheng Qian

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  1. Qiuwei Pan
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  2. Bisheng Liu
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  3. Jin Liu
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  4. Rong Cai
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  5. Yigang Wang
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  6. Cheng Qian
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Correspondence to Cheng Qian.

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Pan, Q., Liu, B., Liu, J. et al. Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL. Mol Cell Biochem 304, 315–323 (2007). https://doi.org/10.1007/s11010-007-9514-6

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  • DOI: https://doi.org/10.1007/s11010-007-9514-6

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