Xu Qian, Liu Gui-Min, Wang Feng-Yun, Zhang Li-Jun, Liang Wen-Tong, Cheng Zhi-Yong
Department of Hematology, the No.1 Hospital of Baoding,Baoding 071000,China.
Nanjing Red Cross Hospital,Nanjing 210001,China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2016 Sep;47(5):669-673.
To investigate the effect of Ruxolitinib on the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 α (HIF-1α) in HEL cells.
he HEL cells were treated with Ruxolitinib in different concentrations (1 nmol/L, 5 nmol/L, 10 nmol/L, 50 nmol/L, 100 nmol/L, 500 nmol/L). The growth inhibition of Ruxolitinib on HEL cells was detected by CCK-8 assay;the mRNA expression level of were measured by RT-PCR and the protein level of p-JAK2, VEGF, HIF-1α were observed by Western blot after treated with Ruxolitinib for 24,48,72 h. Chick chorioallantoic membrane (CAM) test was used to testify the effect of Ruxolitinib on angiogenesis.
Ruxolitinib with different concentrations could inhibit HEL cells proliferation. RT-PCR showed that the mRNA level of decreased in a concentration-dependent manner and Western blot demonstrated that the expression levels of p-JAK2, VEGF and HIF-1α were lower in Ruxolitinib treatment groups than those in control group (<0.05) after HEL cells were treated with different concentrations of Ruxolitinib for 24,48,72 h. Ruxolitinib significantly suppressed blood vessels'formation in CAM.
Ruxolitinib can inhibit VEGF, HIF-1α expression and angiogenesis of HEL leukemia cells by inhibiting JAK2 pathway.
研究鲁索替尼对人红白血病细胞（HEL细胞）中血管内皮生长因子（VEGF）和缺氧诱导因子-1α（HIF-1α）表达的影响。
用不同浓度（1 nmol/L、5 nmol/L、10 nmol/L、50 nmol/L、100 nmol/L、500 nmol/L）的鲁索替尼处理HEL细胞。采用CCK-8法检测鲁索替尼对HEL细胞的生长抑制作用；用RT-PCR检测相关基因的mRNA表达水平，并用蛋白质免疫印迹法观察鲁索替尼处理24、48、72小时后p-JAK2、VEGF、HIF-1α的蛋白水平。采用鸡胚绒毛尿囊膜（CAM）试验验证鲁索替尼对血管生成的影响。
不同浓度的鲁索替尼均可抑制HEL细胞增殖。RT-PCR结果显示，相关基因的mRNA水平呈浓度依赖性降低；蛋白质免疫印迹结果表明，不同浓度鲁索替尼处理HEL细胞24、48、72小时后，鲁索替尼处理组p-JAK2、VEGF和HIF-1α的表达水平均低于对照组（P<0.05）。鲁索替尼可显著抑制CAM中的血管形成。
鲁索替尼可通过抑制JAK2通路抑制HEL白血病细胞的VEGF、HIF-1α表达及血管生成。
