quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting vegfr2 and blocking vegfr2-mediated akt/mtor /p70s6k signaling pathway

نویسندگان

zeng li department of pharmacy, anhui medical university, hefei 230032, china

bin wang department of pharmacy, xiangnan university, chenzhou 423000, china

liang tang department of chirurgery, first affiliated hospital of anhui medical university, hefei 230032, china

shuangsheng chen department of pharmacy, anhui medical university, hefei 230032, china

چکیده

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.

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عنوان ژورنال:
iranian journal of basic medical sciences

جلد ۱۹، شماره ۴، صفحات ۴۱۱-۴۱۶

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