Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24.
OBJECTIVE
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.


CONCLUSIONS
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.
Wu
Yu-mei
YM
Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, China.
Zhang
Kang-jian
KJ
Yue
Xue-tian
XT
Wang
Yi-qiang
YQ
Yang
Yi
Y
Li
Gong-chu
GC
Li
Na
N
Wang
Yi-gang
YG
D000256:Adenoviridae / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D009369:Neoplasms / Q000473:pathology / Q000628:therapy*; D050130:Oncolytic Virotherapy; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D002945:Cisplatin; D007378:Interleukins; D000099180:Interleukin-24