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Abstract
Purpose. Oncolytic adenovirus such as ZD55 has become a promising anticancer agent for its efficient tumor-targeted replication and lysis capability. Armed with therapeutic gene IL-24 to generate a novel oncolytic adenovirus ZD55-IL-24, the antitumor efficiency of ZD55 is greatly increased. To explore the clinical application of ZD55-IL-24 in cancer therapy, the combination of gene-virotherapy (ZD55-IL-24) with chemotherapy was performed in this paper. Methods. The effect of this gene-virotherapy with chemotherapy on cell proliferation was determined by MTT assay in four types of cancer cell lines and one human normal cell line. Real-time PCR was performed to detect the replication of ZD55-IL-24 when adriamycin (ADM) or cisplatin (DDP) was administrated. The changes in caspase pathway were analyzed by Western blot. We further identify the combinational therapy in Balb/c nude mice with NCI-H460 xenograft. Results. ADM and DDP enhanced cell killing/inhibiting effects of ZD55-IL-24 in all the tumor cell lines, while no overlapping toxicity was observed in the normal liver cell line L-02. These chemo-agents inhibited the propagation of ZD55-IL-24 in NCI-H460 cells, but did not influence the expression of IL-24. Consistent with the results in vitro, the tumor growth of co-administration group was remarkably delayed, compared with single treatment groups (p<0.05). Conclusion. ZD55-IL-24 combined with ADM demonstrates improved killing effects against lung tumor xenograft.
Acknowledgements
This work was supported by the Zhejiang Science and Technology Support Plan (No. 2007C33027). The authors would like to thank Kan Chen for her assistance in flow cytometry analysis. We are grateful to Qiang Zhuang and Yuexiang Yin for the technical assistance in qPCR.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.