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

作　　者：PAN Xin-ting ZHU Qing-yun LI De-chun YANG Ji-cheng ZHANG Zi-xiang ZHU Xing-guo ZHAO Hua 

机构地区：[1]Department of General Surgery, First Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215006, China [2]Department of Medical Imaging, Hospital Affiliated to Guiyang Medical College, Guiyang, Guizhou 550000, China [3]Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, Jiangsu 215132, China

出　　处：《Chinese Medical Journal》2008年第20期2031-2036,共6页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the Science Foundation of the Ministry of Health of China （No. WKJ2004-2-011）.

摘　　要：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 1.0×10^10 pfu/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.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 1.0×10^10 pfu/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.

关 键 词：INTERLEUKIN-24 ADENOVIRUS pancreatic carcinoma gene therapy ANGIOGENESIS apoptosis 

分 类 号：R735.9[医药卫生—肿瘤]