甲磺酸氟马替尼对U266细胞株中C-MYC、HIF-1α及VEGF的作用

Effect of Flumatinib Mesylate on C-MYC,HIF-1α and VEGF in U226 Line

本研究旨在探讨新一代酪氨酸激酶抑制剂甲磺酸氟马替尼对多发性骨髓瘤细胞株U266中C-MYC、HIF-1α及VEGF的作用。采用实时荧光定量PCR检测甲磺酸氟马替尼(1、5、10μmol/L)作用于U266细胞株8、16、24h后C-MYC及HIF-1α的表达情况;采用Western blot进一步从蛋白水平检测甲磺酸氟马替尼(1、5、10μmol/L)作用于多发性骨髓瘤细胞株U266 16 h后C-MYC、HIF-1α及VEGF的表达情况。结果表明,C-MYC基因及HIF-1α基因随着氟马替尼作用浓度增大,其表达逐渐降低,差异均具有统计学意义(P<0.05);在相同浓度的氟马替尼作用下,随着药物作用时间的延长其表达逐渐降低,差异均具有统计学意义(P<0.05);C-MYC蛋白、HIF-1α蛋白及VEGF在甲磺酸氟马替尼作用16 h后,随着药物作用浓度的增大,三者表达均逐渐降低,甲磺酸氟马替尼作用前后的差异均有统计学意义(P<0.05)。结论:甲磺酸氟马替尼可以降低U266细胞株中C-MYC、HIF-1α及VEGF的表达,呈时间-剂量依赖性,甲磺酸氟马替尼有可能作为一种治疗MM的新药。

The objective of this study was to investigate the effect of the new generation of tyrosine kinase inhibitor flumatinib mesylate on C-MYC, HIF-1α and VEGF in multiple myeloma（MM） cell line U266. Different concentrations （1, 5,10 μmol/L） of flumatinib mesylate were used to act on U266 cell line for 8, 16 and 24 h, and the expression of C- MYC,and HIF-1α genes was detected by real-time fluorescence-quantitative PCR, the expression of C-MYC, HIF-1α and VEGF was measured by Western blot. The results showed that the gene expression of C-MYC and HIF-1 genes decreased gradually with the increasing of flumatinib mesylate concentration （ P 〈 0.05 ）. At the same concentration of flumatinib mesylate, the expression of C-MYC and HIF-1α gene decreased gradually with prolonging of treatment time with the flumatinib mesylate （P 〈0. 05）. When the flumatinib mesylate acted the U266 cell line for 16 h, the expression of C- MYC, HIF-1α and VEGF decreased gradually with the increasing of flumatinib mesylate concentration （P 〈 0. 05 ）. It is concluded that the flumatinib mesylate can reduce the expression of C-MYC, HIF-1α and VEGF in U266 cell line in a time- and dose-dependent manners, so flumatinib mesylate may become a new drug for MM therapy.