Mechanism of Proliferation and Apoptosis of Acute Promyelocytic Leukemia Cell Line NB4 Induced by TPA.
10.19746/j.cnki.issn.1009-2137.2023.05.007
- Author:
Pan ZHAO
1
;
Chong ZHANG
2
;
Xue-Mei DONG
2
;
Lu-Wei YAN
2
;
Le-Yuan MI
3
,
4
;
Ya-Jiao LI
2
;
Jia-Chao KANG
1
;
Jing WANG
5
Author Information
1. School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China.
2. Clinical Laboratory Center of Gansu Provincial Maternity and Child Care Hospital, Lanzhou 730050, Gansu Province, China.
3. Clinical Laboratory Center of Gansu Provincial Maternity and Child Care Hospital, Lanzhou 730050, Gansu Province, China
4. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu Province, China.
5. School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China E-mail: jwang_2017@hotmail.com.
- Publication Type:Journal Article
- Keywords:
NB4 cell;
acute promyelocytic leukemia;
apoptosis;
phorbol-12-myristate-13-ace-tate;
proliferation
- MeSH:
Humans;
Leukemia, Promyelocytic, Acute;
Caspase 3/metabolism*;
Caspase 9/pharmacology*;
Phosphatidylinositol 3-Kinases/metabolism*;
Proto-Oncogene Proteins c-akt/metabolism*;
bcl-2-Associated X Protein/metabolism*;
Cell Line, Tumor;
Cell Division;
Apoptosis;
RNA, Messenger;
Cell Proliferation
- From:
Journal of Experimental Hematology
2023;31(5):1296-1302
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism.
METHODS:The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT.
RESULTS:Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G1 phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells.
CONCLUSION:TPA induces NB4 cell cycle arrest in G1 phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
