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VEGF Receptor Inhibitor Directly Suppresses Proliferation and Migration of Breast Cancer Cells
Author(s) -
Young Emily,
Tan Wei,
Covington Jordan,
Johnson James Wes,
Gu JianWei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1164.6
Subject(s) - matrigel , umbilical vein , cell growth , receptor , cancer cell , chemistry , cancer research , microbiology and biotechnology , cell migration , cell , endocrinology , angiogenesis , medicine , biology , cancer , in vitro , biochemistry
Recent studies show that certain tyrosine kinase inhibitors target both tumor vasculature and tumor cell. We determine whether the mouse breast cancer cells (E0771) express VEGF receptor‐1 and 2, and whether VEGF receptor inhibitor (SU5416) directly inhibits proliferation and migration of E0771 Cells. Human umbilical vein endothelial cells (HUVEC) and human aortic smooth muscle cells (HASMC) were used as the positive and negative controls. RT‐PCR and Western blot showed that E0771 cells express VEGF receptor‐1 & ‐2 mRNA and protein. 3H‐thymidine incorporation was determined in those cells following exposure to VEGF (10 ng/ml), VEGF plus SU5416 (10 μmol/L) for 18 hrs. VEGF caused a 42% increase in proliferation of E0771 cells, compared to the control (n=6; P<0.01). There was a significant decrease in proliferation of E0771 cells treated with VEGF plus SU5416 vs. the control (65%, P<0.01). VEGF caused a 2‐fold increase in proliferation of HUVEC vs. the control (P<0.01), but its action was completely abolished by SU5416. Neither VEGF nor SU5416 exerted any effect on proliferation of cultured HASMC. Matrigel assay showed that SU5416 (10 μmol/L) inhibited 47% migration of E0771 cells vs. the control (P<0.01). These findings suggest that VEGF receptor inhibitor SU5416 can directly target the breast cancer cells that express VEGF receptor for inhibiting the proliferation and migration. (NIH/AA013821 & NIH/HL51971)