Combined effect of vascular-leakage-blocker Sac-1004 and antiangiogenic drug sunitinib on tumor angiogenesis

Keunho Lee, Vijayendra Agrawal, Kyeojin Kim, Jihye Kim, Hyojin Park, Sungwoon Lee, Young Myeong Kim, Young Ger Suh, Young-Guen Kwon

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Tumor blood vessels are often leaky because of poor covering by mural cells and loose cell-to-cell contacts. Leaky vessels result in hemorrhage and limited vascular perfusion, which lead to hypoxic tumor microenvironment. Antiangiogenic agents have been shown to normalize the tumor blood vessels, albeit temporarily. Continued administration has been found to be associated with increased tumor hypoxia, a major driving force behind chemoresistance and metastasis. Sac-1004 was recently demonstrated to prevent vascular leakage, normalize tumor vessels and prevent metastasis in sustained manner. Here, we sought that combining antiangiogenic agent, sunitinib with Sac-1004 could have better inhibitory effect upon tumor growth. We found that B16F10 tumor growth was significantly reduced and tumor-bearing mice survival was increased upon combining sunitinib therapy with Sac-1004. In concordance with this observation, tumor vascular perfusion was substantially improved in tumors receiving combination therapy. In addition, tumor vascular leakage was reduced to higher extent in combination treatment group as compared to either therapy alone, an effect attributed to improved vascular junction. Interestingly, hypoxia in tumor environment was significantly reduced, when sunitinib was combined with Sac-1004. Taken together, our data demonstrates that combining antiangiogenic therapy with vascular-leakage inhibiting agent might be a beneficial strategy to combat cancer.

Original languageEnglish
Pages (from-to)1320-1326
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume450
Issue number4
DOIs
Publication statusPublished - 2014 Aug 8

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Blood Vessels
Tumors
Pharmaceutical Preparations
Neoplasms
Vascular Tissue Neoplasms
Angiogenesis Inhibitors
Perfusion
Blood vessels
Neoplasm Metastasis
Tumor Microenvironment
sunitinib
Sac-1004
Bearings (structural)
Therapeutics
Growth
Hemorrhage

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Lee, Keunho ; Agrawal, Vijayendra ; Kim, Kyeojin ; Kim, Jihye ; Park, Hyojin ; Lee, Sungwoon ; Kim, Young Myeong ; Suh, Young Ger ; Kwon, Young-Guen. / Combined effect of vascular-leakage-blocker Sac-1004 and antiangiogenic drug sunitinib on tumor angiogenesis. In: Biochemical and Biophysical Research Communications. 2014 ; Vol. 450, No. 4. pp. 1320-1326.
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Combined effect of vascular-leakage-blocker Sac-1004 and antiangiogenic drug sunitinib on tumor angiogenesis. / Lee, Keunho; Agrawal, Vijayendra; Kim, Kyeojin; Kim, Jihye; Park, Hyojin; Lee, Sungwoon; Kim, Young Myeong; Suh, Young Ger; Kwon, Young-Guen.

In: Biochemical and Biophysical Research Communications, Vol. 450, No. 4, 08.08.2014, p. 1320-1326.

Research output: Contribution to journalArticle

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