In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer

Takahiro Koyanagi, Yasuhiro Suzuki, Yasushi Saga, Shizuo Machida, Yuji Takei, Hiroyuki Fujiwara, Mitsuaki Suzuki, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1705-1710
Number of pages6
JournalCancer science
Volume104
Issue number12
DOIs
Publication statusPublished - 2013 Dec

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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