Inhibition of ovarian tumor growth by gene therapy with recombinant soluble vascular endothelial growth factor receptor 2.
The growth and persistence of solid tumors and their metastases are angiogenesis dependent. Targeting angiogenesis represents a new strategy for the development of antitumor therapies. The extracellular immunoglobulin- like domain of VEGFR-2 (KDR/Flk-1), soluble VEGFR-2, may form a heterodimeric complex with a wild-type VEGF receptor and function as a dominant negative receptor. We assessed the effects of sFlk-1 on SKOV3 cell growth and proliferation in vitro. Furthermore, we investigated the effectiveness of recombinant soluble Flk-1 adenovirus on inhibition of tumor growth in an ovarian tumor (SKOV3) nude murine model, combined with cis-diamminedichloroplatinum (DDP). Nude mice bearing SKOV3 tumors received adsFlk- 1 (recombinant soluble Flk-1 adenovirus) and DDP, respectively or in combination, and tumor growth inhibition, microvessel density, and apoptosis in tumor tissue were assessed by immunohistochemical analysis. Our data revealed that sFlk-1 had little effect on tumor cell growth in vitro, whereas ad-sFlk-1 administration could inhibit tumor growth significantly (p < 0.05) in the nude murine model, accompanied by angiogenesis suppression and apoptosis induction, and augmented efficiency was observed in combination with DDP as well. The present findings suggest that gene therapy with ad-sFlk-1 is an efficient antiangiogenesis strategy, which may be important in further exploration and possible translation into a clinical trial.
Wu
Ying
Y
Department of Gynecology and Obstetrics, West China Second Hospital of Sichuan University, Chengdu 610041, People's Republic of China.
Li
Zheng-Yu
ZY
Zhao
Xia
X
Kan
Bing
B
Wei
Yu-Quan
YQ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D020287:In Situ Nick-End Labeling; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000627:therapeutic use*
D011994:Recombinant Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2