Effects of Paclitaxel and Quizartinib Alone and in Combination on AML Cell Line MV4-11 and Its STAT5 Signal Pathway.
10.19746/j.cnki.issn.1009-2137.2022.03.003
- Author:
Zi-Wen BAI
1
;
Mei-Qing WU
1
;
Bao-Wen ZHOU
1
;
Ze-Yan SHI
1
;
Yi-Bin YAO
1
;
Zhen-Fang LIU
1
;
Ru-Li PANG
1
;
Wei-Hua ZHAO
2
Author Information
1. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China.
2. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China,E-mail: zhaowh21@163.com.
- Publication Type:Journal Article
- Keywords:
FLT3/STAT5;
leukemia;
paclitaxel;
quizatinib
- MeSH:
Apoptosis;
Benzothiazoles;
Cell Line, Tumor;
Humans;
Leukemia, Myeloid, Acute/genetics*;
Paclitaxel/therapeutic use*;
Phenylurea Compounds;
RNA, Messenger;
STAT5 Transcription Factor/pharmacology*;
Signal Transduction;
fms-Like Tyrosine Kinase 3
- From:
Journal of Experimental Hematology
2022;30(3):671-676
- CountryChina
- Language:Chinese
-
Abstract:
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.
