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.
Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2022 Jun;30(3):671-676. doi: 10.19746/j.cnki.issn.1009-2137.2022.03.003.
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+).
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.
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).
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.
探讨紫杉醇、奎扎替尼及其联合应用对人白血病细胞系MV4-11（FLT3-ITD+）增殖、凋亡及FLT3/STAT5通路的影响。
分别用不同浓度的紫杉醇和奎扎替尼处理MV4-11细胞24小时、48小时和72小时，然后在48小时时将两种药物联合使用，比较对增殖的抑制作用，通过流式细胞术检测凋亡率，用荧光定量PCR测定FLT3和STAT5 mRNA的表达，用蛋白质免疫印迹法测定FLT3、p-FLT3、STAT5和p-STAT5的蛋白表达。
紫杉醇和奎扎替尼不同联合组具有协同抑制作用。联合组细胞存活率明显低于单药组（P<0.05）。联合组细胞凋亡率明显高于单药组（P<0.001）。联合组FLT3 mRNA表达明显高于两种单药组（P<0.01）。联合组STAT5 mRNA表达明显高于奎扎替尼组（P<0.001）；与紫杉醇组相比有所升高，但无统计学意义。联合组p-FLT3、p-STAT5蛋白表达水平明显低于单药组（P<0.05，P<0.05）。
紫杉醇联合奎扎替尼可协同抑制MV4-11细胞系增殖，并通过抑制FLT3/STAT5通路活性促进MV4-11细胞系凋亡。
