Treatment of pancreatic carcinoma by adenoviral mediated gene transfer of vasostatin in mice

¹ Department of Gastroenterology, Ruijin Hospital, Shanghai Second Medical University, China
² Department of Biochemistry and Center of Human Gene Therapy, Shanghai Second Medical University, China

^* To whom correspondence should be addressed. E-mail: yyz28{at}medmail.com.cn.

Accepted 28 September 2005

	Abstract

Background: Tumor growth is angiogenesis- dependent and antiangiogenesis therapy may represent a promising therapeutic option.

Aims: To evaluate the inhibitory effect of vasostatin gene mediated by a replication-deficient recombinant adenovirus on human pancreatic cancer in vivo and to investigate the mechanism of vasostatin.

Methods: Human umbilical vein endothelium derived ECV304 cells were infected with Ad-vasostatin and Ad- lacZ, compared with PBS. MTT assay was used to estimate the proliferation of ECV304 cells; tube formation assay and choriallantoic membrance assay were used to evaluate angiogenesis in vitro and in vitro. The xenografted nude mice with pancreatic cancer were established to observe the in vivo tumor growth suppression. The microvessel density revealed by CD31 immunohistochemical staining was measured.

Results: The growth and tube formation of ECV304 cells infected with Ad-vasostatin was suppressed significantly compared with that of cells infected with Ad-lacZ or cells treated with PBS. The neovascularization in Ad-vasostatin group was less than these in PBS group and in Ad-lacZ group according to the CAM results. The volumes of pancreastic tumors in Ad- vasostatin group were smaller significantly than these in PBS group and in Ad-lacZ group at the end of the treatment period. The microvessel density of the Ad- vasostatin group was significantly lower than that of the Ad-lacZ group and the PBS group.

Conclusion: The vasostatin gene mediated by adenovirus is efficient for gene therapy for pancreatic carcinoma. The suppression of vasostatin on the proliferation of vasocular endothelium cells and angiogenesis may account for its effect.

Keywords: adenoviral vectors, antiangiogenesis, gene therapy, pancreatic neoplasms, vasostatin

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