紫杉醇和奎扎替尼单药及其联用对AML细胞株MV4-11及其STAT5信号通路的作用  

Effects of Paclitaxel and Quizartinib Alone and in Combination on AML Cell Line MV4-11 and Its STAT5 Signal Pathway

作　　者：白子文 吴梅青 周宝文 石泽延[1] 姚奕斌[1] 刘振芳[1] 庞如利 赵卫华[1] BAI Zi-Wen;WU Mei-Qing;ZHOU Bao-Wen;SHI Ze-Yan;YAO Yi-Bin;LIU Zhen-Fang;PANG Ru-Li;ZHAO Wei-Hua(Department of Hematology,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China)

机构地区：[1]广西医科大学第一附属医院血液内科,广西南宁530000

出　　处：《中国实验血液学杂志》2022年第3期671-687,共17页Journal of Experimental Hematology

基　　金：中国博士后科学基金第67批面上项目(2020M673097);广西壮族自治区卫生健康委员会自筹经费科研课题(Z20200961)。

摘　　要：目的:探讨紫杉醇、奎扎替尼单药及二者联合对人白血病细胞株MV4-11(FLT3-ITD;)增殖、凋亡的影响,以及对FLT3/STAT5通路的作用。方法:分别用不同浓度紫杉醇、奎扎替尼单药作用于MV4-11细胞24、48、72 h,在48 h时间点两种药物分别选取两种浓度联合使用,比较细胞增殖抑制情况;选用一种药物浓度组合用流式细胞术检测细胞凋亡率,荧光定量PCR法测定FLT3、STAT5 mRNA表达水平,Western blot法测定FLT3、p-FLT3、STAT5、p-STAT5蛋白的表达水平。结果:不同的紫杉醇、奎扎替尼联合用药组均有协同抑制作用,联合用药组的细胞存活率明显低于单药组(P<0.05),联合用药组细胞的凋亡率均明显高于单药组(P<0.001)。联合用药组FLT3 mRNA的表达量均显著高于单药组(P<0.001);联合用药组STAT5 mRNA的表达量高于奎扎替尼单药组(P<0.01),但与紫杉醇单药组比较差异无统计学意义。联合用药组p-FLT3、p-STAT5蛋白的表达水平均显著低于单药组(P<0.05,P<0.05)。结论:紫杉醇联合奎扎替尼可以协同抑制MV4-11细胞株的增殖,可能通过抑制FLT3/STAT5通路活性促进MV4-11细胞株凋亡。Objective: To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11(FLT3-ITD;). Methods: MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot. Results: Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group(P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group(P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs(P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group(P<0.001);increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group(P<0.05, P<0.05). Conclusion: Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.

关 键 词：白血病 紫杉醇 奎扎替尼 FLT3/STAT5 

分 类 号：R733.71[医药卫生—肿瘤]