title: Cancer targeting gene-viro-therapy for pancreatic cancer using oncolytic adenovirus ZD55-IL-24 in immune-competent mice.
abstract: Cancer targeting gene-viro-therapy (CTGVT) may prove to be an effective treatment for pancreatic cancer (PC). This study was intended to explore the anti-tumor effect of ZD55-IL-24 (oncolytic adenovirus ZD55 harboring IL-24) on PC in immune-competent mice. The expression of gene harbored by oncolytic adenovirus ZD55 in PC cells was detected by reporter-gene assays. The in vitro anti PC ability of ZD55-IL-24 was tested by MTT, crystal violet staining and apoptosis assays. The in vivo anti PC effect of ZD55-IL-24 was further observed in an immune-competent mice model by detecting anti-tumor immunity and induction of apoptosis. The expression of gene harbored by ZD55 in PC cells was significantly higher than that harbored by the replicated-deficient adenovirus, and the amount of gene expression was time-dependent and dose-dependent. Both ZD55-IL-24 and ZD55 inhibited PC cells growth, but the anti-tumor effect of ZD55-IL-24 was significantly stronger than that of ZD55, and the ability of ZD55-IL-24 in inducing PC apoptosis was significantly stronger than that of ZD55. The tumor-forming rate of group ZD55-IL-24 was the lowest, and the tumor-growing rate was also significantly lower than that of group ZD55 in immune-competent PC models. Moreover, ZD55-IL-24 mediated more anti-cancer immunity effects by induction of stronger T-lymphocytes response to PC cells, higher levels of γ-IFN and IL-6 cytokines. ZD55-IL-24-mediated CTGVT could inhibit PC growth not only by inducing oncolysis and apoptosis but enhancing the anti-cancer immune effects by inducing T cell response to PC and up-regulating γ-IFN and IL-6 cytokine in immune-competent mice. This may serve as a candidate therapeutic approach for the treatment of PC.
authors.affiliation: Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Kongjiang Road 1665, Shanghai, 200092, China. 15000330960@139.com
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Huang
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D005840:Gentian Violet; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D050130:Oncolytic Virotherapy / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D000099180:Interleukin-24
chemical_list: D016207:Cytokines; D005840:Gentian Violet; D007371:Interferon-gamma; D007378:Interleukins; D013778:Tetrazolium Salts; D013844:Thiazoles; D000099180:Interleukin-24; C022616:thiazolyl blue