An armed oncolytic adenovirus ZD55-IL-24 combined with ADM or  DDP demonstrated enhanced antitumor effect in lung cancer.
OBJECTIVE
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).


CONCLUSIONS
ZD55-IL-24 combined with ADM demonstrates improved killing effects against lung tumor xenograft.
Zhong
Suyang
S
Xin Yuan Institute of Medicine and Biotechnology, Life Science College, Zhejiang Sci-Tech University, Hangzhou 310018, China.
Yu
Debin
D
Wang
Yigang
Y
Qiu
Songbo
S
Wu
Songjie
S
Liu
Xin Yuan
XY
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015153:Blotting, Western; D024201:Bystander Effect; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D003131:Combined Modality Therapy / Q000379:methods; D004317:Doxorubicin / Q000008:administration & dosage*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D020287:In Situ Nick-End Labeling; D007378:Interleukins / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D002945:Cisplatin; D004317:Doxorubicin; D007378:Interleukins; D000099180:Interleukin-24