Abstract
Acquired resistance to anti-angiogenetic drugs have emerged as a potentially important problem in clinical settings, however, the underlying mechanism remains largely unclear. In this study, we established human umbilical vein endothelial cell (HUVEC) clones that are resistant to VEGFR tyrosine kinase inhibitor (VEGFR-TKI, Ki8751) using MNNG and VEGFR-TKI.
In growth inhibition assay, VEGFR-TKI resistant HUVEC clones were significantly decreased cellular sensitivity to Ki8751 about 4-10 fold compared with that in the parental cells. VEGF-mediated cellular proliferations of resistant clones were also decreased. Interestingly, VEGFR2 expression was down-regulated and the phosphorylation levels of Akt were up-regulated in resistant clones. Finally, microarray analysis revealed that several angiogenesis-related or -specific genes including CD31 were remarkably down-regulated in resistant clones compared with the parental cells. In conclusion, these results suggest that the mechanism of VEGFR-TKI resistant is closely involved in “escape phenomenon” from VEGF-VEGFR system and our findings provide a novel insight into the drug resistant to VEGFR-TKI in vascular endothelial cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 370.
- ©2010 American Association for Cancer Research
Volume 70, Issue 8 Supplement
