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Carcinogenesis Advance Access published online on June 17, 2004
Carcinogenesis, doi:10.1093/carcin/bgh216
© 2004 by Oxford University Press
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Received February 26, 2004
Revised May 19, 2004
Accepted June 10, 2004

CANCER BIOLOGY

Antiangiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts

Manoj Kumar 1, Zheng-Ren Liu 1, Laxmi Thapa 2, Ren-Yi Qin 1*

1 Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China
2 Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, China

* To whom correspondence should be addressed. E-mail: ryqin{at}tjh.tjmu.edu.cn.


  Abstract

Somatostatin receptor subtypes, especially subtype 2 (SSTR2), exert their antitumor (cytostatic and/or cytotoxic) and antiangiogenic effects. Here we aimed to investigate the antiangiogenic effect of SSTR2 gene transfer into pancreatic cancer cell line PC-3, and the mechanisms involved in this effect. The full length human SSTR2 cDNA was introduced into pancreatic cancer cell line PC-3 by lipofectamine-mediated transfection, and stable expression of SSTR2 was detected by immunohistochemistry and RT-PCR. Athymic mice were separately xenografted with SSTR2-expressing cells (experimental group), vector control and mock control cells. Intratumoral microvessel density (MVD) was assessed by immunohistochemistry. Immunohistochemistry and RT-PCR were used to determine the expression of angiogenic factors VEGF, bFGF, and MMP-2 in xenograft tumors. MVD was significantly lower in the experimental group (5.16±1.34) than that in the vector control (16.52±2.25) and mock control (15.32±2.53) (P<0.05). The immunohistochemical assay showed a significant decrease in the expression of VEGF, bFGF, and MMP-2 protein in the experimental group compared to the vector control and mock control, considering both the integral optical density and area of staining (P<0.05). RT-PCR showed a significant reduction of VEGF, bFGF and MMP-2 mRNA expression in the experimental group compared with the vector control and mock control (P<0.05). Thus introduction of SSTR2 gene, the expression of which is frequently lost in human pancreatic adenocarcinoma, exerts its antiangiogenic effects by down-regulating the expression of the factors, which are involved in tumor angiogenesis and metastasis, suggesting SSTR2 gene transfer as a promising strategy of gene therapy for pancreatic cancer.


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