title: In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer.
abstract: Vasohibin-2 (VASH2) is a homolog of vasohibin-1 and exhibits pro-angiogenic activity. We recently reported that VASH2 is expressed in certain ovarian cancers and promotes tumor growth through angiogenesis. To further demonstrate the effectiveness of molecular targeting of VASH2 for anticancer treatment, we applied in vivo delivery of siRNA targeting VASH2 (siVASH2) using atelocollagen to a xenograft model of ovarian cancer. We inoculated mice s.c. with DISS and SKOV-3, two representative human ovarian serous adenocarcinoma cell lines. When tumors were measurable, we initiated treatment with control or siVASH2 mixed with atelocollagen, which enveloped the whole tumor. Treatment with siVASH2 significantly inhibited s.c. tumor growth by abrogating tumor angiogenesis. We confirmed that expression of VASH2 mRNA in the tumor was downregulated by siVASH2 treatment. In addition, the siVASH2-treated tumor contained more blood vessels covered with pericytes, indicating that knockdown of VASH2 contributes to the normalization of tumor blood vessels. Based on these results, VASH2 may be a promising molecular target for ovarian cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Jichi Medical University, Tochigi, Japan; Department of Vascular Biology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Koyanagi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Saga
authors.forename: Shizuo
authors.initials: S
authors.lastname: Machida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takei
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D058990:Molecular Targeted Therapy / Q000379:methods*; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000628:therapy*; D010051:Ovarian Neoplasms / Q000098:blood supply* / Q000628:therapy*; D020286:Pericytes / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D042501:Angiogenic Proteins; D034741:RNA, Small Interfering; C574858:VASH2 protein, human; C059821:atelocollagen; D003094:Collagen