Research of venetoclax in the treatment of acute myeloid leukemia
10.13699/j.cnki.1001-6821.2024.24.013
- VernacularTitle:维奈克拉治疗急性髓系白血病的研究
- Author:
Su-qing GUO
1
;
Rui SHI
;
Yan WU
;
Ying-hua LI
;
Hui-ling MIAO
Author Information
1. 衡水市人民医院血液内科,河北衡水 053000
- Publication Type:Journal Article
- Keywords:
venetoclax;
acute myeloid leukemia;
monocyte;
cell proliferation;
apoptotic protein;
Tyr-3/Trp-5 monooxygenase activation protein gamma
- From:
The Chinese Journal of Clinical Pharmacology
2024;40(24):3585-3589
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism of venetoclax(Vene)in the treatment of acute myeloid leukemia(AML).Methods THP1 cells were divided into control group(normal culture),experimental group(100 nmol·L-1 Vene treatment),NC mimics group(100 nmol·L-1 Vene treatment+transfection simulator negative control)and miR-181a mimics group(100 nmol·L-1Vene treated+transfected miR-181a mimic),NC mimics combined with pcDNA3.1-NC group[100 nmol·L-1 Vene treated+transfected mimic negative control+transfected Tyr-3/Trp-5 monooxygenase activation protein gamma(YWHAG)negative control],miR-181a mimics combined with pcDNA3.1-NC group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected YWHAG negative control),Vene+miR-181a mimics+pcDNA3.1-YWHAG group(100 nmol·L-1 Vene treated+transfected miR-181a mimic+transfected pcDNA3.1-YWHAG).Real-time quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression of miR-181a and YWHAG mRNA relative expression level;the positive expression of YWHAG was detected by immunofluorescence;the cell proliferation levels was detected by 5-acetylidene-2'deoxyuracil riboside(EdU)assay;the expression of B-cell lymphoma factor 2(Bel-2)and Bel-2 associated X protein(Bax)were detected by Western blot.Results The relative expression of miR-181a in control group,experimental group,NC mimics group and miR-181a mimics group were 1.00±0.14,0.43±0.05,0.47±0.06 and 0.85±0.11,respectively;the relative mRNA expression level of YWHAG were 1.00±0.16,2.13±0.21,2.35±0.28 and 1.37±0.17,respectively.The above indexes of the experimental group were statistically significant compared with the control group,and the above indexes of the NC mimics group were statistically significant compared with the miR-181a mimics group(all P＜0.01).The relative expression levels of YWHAG in NC mimics combined with pcDNA3.1-NC group,miR-181a mimics combined with pcDNA3.1-NC group,Vene+miR-181a mimics+pcDNA3.1-YWHAG group were 1.00±0.13,0.77±0.10 and 0.93±0.14;the proliferation rates were(18.27±3.55)％,(43.19±7.20)％and(28.41±5.84)％,respectively;the relative expression levels of Bel-2 protein were 1.00±0.19,2.23±0.42 and 1.17±0.25,respectively;the relative expression levels of Bax protein were 1.00±0.17,0.39±0.06 and 0.78±0.11,respectively.The above indexes of miR-181a mimics combined with pcDNA3.1-NC group were compared with those of NC mimics combined with pcDNA3.1-NC group,and the above indexes of Vene+miR-181a mimics+pcDNA3.1-YWHAG group were compared with those of miR-181 a mimics combined with pcDNA3.1-NC group,the differences were statistically significant(all P＜0.05).Conclusion The treatment of Vene in acute myeloid leukemia may be realized by regulating miR-181a targeting YWHAG,thereby inhibiting monocyte proliferation and promoting cell apoptosis.
