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 language | English |
|---|---|
| Pages (from-to) | 1320-1326 |
| Number of pages | 7 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 450 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 Aug 8 |
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All Science Journal Classification (ASJC) codes
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
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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 journal › Article
TY - JOUR
T1 - Combined effect of vascular-leakage-blocker Sac-1004 and antiangiogenic drug sunitinib on tumor angiogenesis
AU - Lee, Keunho
AU - Agrawal, Vijayendra
AU - Kim, Kyeojin
AU - Kim, Jihye
AU - Park, Hyojin
AU - Lee, Sungwoon
AU - Kim, Young Myeong
AU - Suh, Young Ger
AU - Kwon, Young-Guen
PY - 2014/8/8
Y1 - 2014/8/8
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2014.06.139
DO - 10.1016/j.bbrc.2014.06.139
M3 - Article
VL - 450
SP - 1320
EP - 1326
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -