@article { author = {Li, Zeng and Wang, Bin and Tang, Liang and Chen, Shuangsheng and Li, Jun}, title = {Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR2 and blocking VEGFR2-mediated Akt/mTOR /p70s6k signaling pathway}, journal = {Iranian Journal of Basic Medical Sciences}, volume = {19}, number = {4}, pages = {411-416}, year = {2016}, publisher = {Mashhad University of Medical Sciences}, issn = {2008-3866}, eissn = {2008-3874}, doi = {10.22038/ijbms.2016.6813}, abstract = {Objective(s): We previously reported a series of quinazoline derivatives as vascular-targeting anticancer agents. In this study, we investigated the mechanism underlying the anti-angiogenic activity of the quinazoline derivative compound 11d. Materials and Methods: We examined the effects of quinazoline derivative 11d on vascular endothelial growth factor receptor-2 (VEGFR2) activation via VEGFR2-specific activation assay. Reverse transcription and immunohistochemistry were used to detect vascular endothelial growth factor (VEGF), VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in human umbilical vascular endothelial cells and hepatocellular carcinoma cells (HepG-2) after treatment with various concentrations of 11d (0, 6.25, 12.5, and 25 μM) for 24 hr. Results: The compound 11d exhibited potent inhibitory activity against VEGFR2 with an IC50 of 5.49 μM. This compound significantly downregulated VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway in vitro. Conclusion:The mechanism underlying the anti-angiogenic activity of the quinazoline derivative 11d possibly involves the inhibition of VEGFR2 and the downregulation of VEGF, VEGFR2, and the VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway. Overall, the findings indicate that the studied class of compounds is a source of potential antiproliferative and anti-angiogenic agents, which must be further investigated.}, keywords = {anti-angiogenic Akt/mTOR/p70s6k mechanism,Quinazoline derivatives,VEGF,VEGFR2}, url = {https://ijbms.mums.ac.ir/article_6813.html}, eprint = {https://ijbms.mums.ac.ir/article_6813_9d85d0e6f2dc562b4ee1095e18163132.pdf} }