Effect of recombinant adenovirus vector mediated human interleukin-24 gene transfection on pancreatic carcinoma growth

Background Pancreatic cancer is a highly malignant tumor affecting an ever increasing number of patients with a mean 5-year survival rate below 4%.Therefore,gene therapy for cancer has become a potential novel therapeutic modality.In this study we sought to determine the inhibitory effects of adenovirus-mediated human interleukin-24 （AdhIL-24）on pancreatic cancer. Methods Human interleukin-24 gene was cloned into replication-defective adenovirus specific for patu8988 tumor cells by virus recombination technology.Reverse transcription-polymerase chain reaction and Western blotting analysis were used to determine the expression of human interleukin-24 mRNA in patu8988 cells in vitro.Induction of apoptosis by overexpression of human interleukin-24 in patu8988 cells was determined by flow cytometry.In vivo efficacy of adenoviral delivery of human interleukin-24 was assessed in nude mice（n=10 for each group）bearing patu8988 pancreatic cancer cell lines by determining inhibition of tumor growth,endothelial growth factor and CD34 expression, and intratumoral microvessel density（MVD）. Results The recombinant adenovirus vector AdVGFP/IL-24 was constructed with a packaged recombinant retrovirus titer of 1.0×10pfu/ml and successfully expressed of both mRNA and protein in patu8988 cells.The AdVGFP/IL-24 induced apoptosis of patu8988 tumor cells in vitro and significantly inhibited tumor growth in vivo（P<0.05）.The intratumoral MVD decreased significantly in the treated tumors（P<0.05）. Conclusion The recombinant adenovirus AdGFP/IL-24 can effectively express biologically active human interleukin-24, which results in inhibition of pancreatic cancer growth.