Position：Vice Chair of Pharmacy
Department：Pharmacy
Medical School：Zhejiang University School of Medicine, China
Academic Rank：Chief Pharmacist
Tumor pharmacology; effects and mechanisms of Rac1 on endothelial cell in lung cancer metastasis.
Leadership Award of Zhejiang Province Pharmaceutical Administration
Senior Member, Chinese Pharmaceutical Association
Member, Editor Board, Chinese Journal of Modern Applied Pharmacy
A variety of vasoactive stimuli induce endothelial permeability through Rac1, a membrane of Rho small GTPases. Dr. Zhang's research team found that activation of Rac1 was assayed in human umbilical vein endothelial cells (HUVEC), transendothelial passages were measured by Transwell chambers, and hematogenously metastatic mouse model was generated by intravenous injection with Lewis lung carcinoma cells (LLC). LLC secreted abundant vascular endothelial growth factor (VEGF) in the culture media and sera of mice bearing LLC xenografts or metastatic LLC, and VEGF activated Rac1 through VEGF receptors/PI3Kβ signaling cascade, resulting in hyperoxidative stress and consequent hyperpermeability in HUVEC. Moreover, in co-culture of LLC and HUVEC, significant increases in endothelial permeability and transendothelial migration of LLC were robustly attenuated by either anti-VEGF neutralizing antibody or Rac1 knockdown in HUVEC. Finally, in metastatic mouse model, deletion of one copy of Rac1 in endothelium not only significantly attenuated LLC-induced vascular permeability, but robustly reduced the metastasis of LLC to lungs.
Ruan H, Luo H, Wang J, Ji X, Zhang Z, Wu J, Zhang X, Wu X. Smoothened-independent activation of hedgehog signaling by rearranged during transfection promotes neuroblastoma cell proliferation and tumor growth. Biochimica et biophysica acta 2016, 1860(9):1961-1972.
Yao H, Shi W, Wu J, Xu C, Wang J, Shao Y, Wu X, Zhang Z. Endothelial Rac1 is essential for hematogenous metastasis to the lung. Oncotarget 2015, 6(19):17501-17513.
Yan XF, Zhang ZM, Yao HY, Guan Y, Zhu JP, Zhang LH, Jia YL, Wang RW. Cardiovascular protection and antioxidant activity of the extracts from the mycelia of Cordyceps sinensis act partially via adenosine receptors. Phytotherapy Research : PTR 2013, 27(11):1597-1604.
Li W, Xu H, Hu Y, He P, Ni Z, Xu H, Zhang Z, Dai H. Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress. PloS One 2013, 8(9):e76025.
Ni Z, Zhuge Z, Li W, Xu H, Zhang Z, Dai H. Inhibitory effects of hydroxysafflor yellow A on the formation of advanced glycation end products in vitro. Biological & Pharmaceutical Bulletin 2012, 35(11):2050-2053.
Zhao HW, Lu Y, Li XY, Xu ZH, Zhang ZM, Hu WW, Chen Z. Intranasal administration of low dosage recombinant human erythropoietin inhibits seizure in rats. Journal of Zhejiang University Medical Sciences 2009, 38(6):565-571.
Xu DH, Lou HG, Yuan H, Jiang B, Zhou Q, Zhang ZM, Ruan ZR. Quantitative determination of domperidone in human plasma by ultraperformance liquid chromatography with electrospray ionization tandem mass spectrometry. Biomedical Chromatography: BMC 2008, 22(4):433-440.
Zhou Q, Yan XF, Zhang ZM, Pan WS, Zeng S. Rational prescription of drugs within similar therapeutic or structural class for gastrointestinal disease treatment: drug metabolism and its related interactions. World Journal of Gastroenterology 2007, 13(42):5618-5628.
Dai H, Fu Q, Shen Y, Hu W, Zhang Z, Timmerman H, Leurs R, Chen Z. The histamine H3 receptor antagonist clobenpropit enhances GABA release to protect against NMDA-induced excitotoxicity through the cAMP/protein kinase A pathway in cultured cortical neurons. European Journal of Pharmacology 2007, 563(1-3):117-123.
Dai H, Zhang Z, Zhu Y, Shen Y, Hu W, Huang Y, Luo J, Timmerman H, Leurs R, Chen Z. Histamine protects against NMDA-induced necrosis in cultured cortical neurons through H receptor/cyclic AMP/protein kinase A and H receptor/GABA release pathways. Journal of Neurochemistry 2006, 96(5):1390-1400.
Effects and mechanisms of Rac1 on endothelial cell in lung cancer metastasis. Funding Source: National Natural Science Foundation of China.
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