Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24
| Autor: | Yigang Wang, Gongchu Li, Yi Yang, Na Li, Yi-qiang Wang, Yu-mei Wu, Kang-jian Zhang, Xue-tian Yue |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Oncolytic adenovirus
Antineoplastic Agents Apoptosis Flow cytometry Adenoviridae Cell Line Neoplasms medicine Cytotoxic T cell Humans Pharmacology (medical) MTT assay Pharmacology Cisplatin Oncolytic Virotherapy medicine.diagnostic_test Dose-Response Relationship Drug business.industry Interleukins General Medicine Genetic Therapy Virology Combined Modality Therapy Oncolytic virus Cancer cell Cancer research Original Article business medicine.drug |
| Zdroj: | Acta pharmacologica Sinica. 30(4) |
| ISSN: | 1745-7254 |
| Popis: | 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. 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. 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. 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. |
| Databáze: | OpenAIRE |
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