Multiple drug resistance phenotype of human endothelial cells induced by vascular endothelial growth factor 165.
OBJECTIVE
To investigate the effect of vascular endothelial growth factor 165 (VEGF165) on sensitivity of endothelial cells to anticancer drugs.


METHODS
Human dermal microvessel endothelial cells (HDMEC) were incubated with anticancer drugs in the presence of VEGF165. Survival of endothelial cells was assayed by MTT method. DNA fragments of apoptosis were detected by agarose electrophoresis. Potential mechanisms underlying the effect of VEGF165 on endothelial cells were investigated with RT-PCR and Western blot analysis.


RESULTS
VEGF165 induced the multidrug resistance phenotype of HDMEC to a wide variety of anticancer drugs such as epirubicin, cisplatin, etoposide, mytomycin C, vincristine, CPT-11, and taxol in vitro. This protective effect was partly due to the up-regulation of lung drug resistance protein (LRP) and multidrug resistance-associated protein (MRP), as well as the down-regulation of Bax protein induced by VEGF165.


CONCLUSIONS
VEGF165 induced multidrug resistance phenotype of endothelial cells, which implicated the anti-angiogenic effect of anticancer drugs might depend on microenvironment of tumors in vivo.
Zhang
X S
XS
Cancer Center, Sun Yat-sen University of Medical Sciences, Guangzhou 510060, China.
Zhu
X F
XF
Gao
J S
JS
Qian
C N
CN
Kuang
Z J
ZJ
Liu
Z C
ZC
Zeng
Y X
YX
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002196:Capillaries / Q000166:cytology / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D015251:Epirubicin / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D017239:Paclitaxel / Q000494:pharmacology; D010641:Phenotype; D012867:Skin / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D015251:Epirubicin; D000077146:Irinotecan; D017239:Paclitaxel; D002166:Camptothecin