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 x 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).


CONCLUSIONS
The recombinant adenovirus AdGFP/IL-24 can effectively express biologically active human interleukin-24, which results in inhibition of pancreatic cancer growth.
Pan
Xin-ting
XT
Department of General Surgery, First Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215006, China.
Zhu
Qing-yun
QY
Li
De-chun
DC
Yang
Ji-cheng
JC
Zhang
Zi-xiang
ZX
Zhu
Xing-guo
XG
Zhao
Hua
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D015153:Blotting, Western; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D000099180:Interleukin-24
D018952:Antigens, CD34; D007378:Interleukins; D042461:Vascular Endothelial Growth Factor A; D000099180:Interleukin-24