Reversal of Drug Resistance in K562/ADM Cells Caused by RA and the Related Mechanisms.
10.19746/j.cnki.issn.1009-2137.2021.06.002
- Author:
Si-Si ZHONG
1
;
Yong-Ping YUAN
2
;
Liu-Yan XIN
2
;
Yi-Jian CHEN
3
;
Li-Qun ZHANG
4
Author Information
1. Department of Quality and Safety Management, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China.
2. Department of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China.
3. Department of Hematology, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China,E-mail: chenyj2005@163.com.
4. Department of Quality and Safety Management, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, Jiangxi Province, China,E-mail: 176784620@qq.com.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Subfamily B;
ATP Binding Cassette Transporter, Subfamily B, Member 1;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
Humans;
K562 Cells
- From:
Journal of Experimental Hematology
2021;29(6):1704-1709
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effect of ursane triterpenoids 3β,19α-dihydroxyursu-12-ene-23,28-dicarboxylic acid (Rotundioic acid, RA) on the sensitivity of adriamycin-resistant K562 cells (K562/ADM Cell) anti-tumor drug, and to explore the effect and mechanism of RA on the multidrug resistance of K562/ADM cells.
METHODS:CCK-8 method was used to detect the effect of RA on the sensitivity of K562 cells and K562/ADM cells to anti-tumor drug. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression level of mRNA and the protein in K562 and K562/ADM cells, and the effect of RA on the expression of MDR1 mRNA and P-gp in K562/ADM cells was also detected; Western blot was used to detect the expression of p-JNK, p-p38 and p-ERK1/2 in K562/ADM cells.
RESULTS:RA could increased the sensitivity of K562/ADM cells to adriamycin(the reversal factor was 1.61 times), the difference showed statistically significantly (P<0.05); the resistance factor of K562/ADM to ADM was 41.76 times. The expression of MDR1 mRNA in K562 cells was extremely low, and the protein product P-glycoprotein (P-gp) was almost not expressed; MDR1 mRNA and P-gp in K562/ADM cells were highly expressed; RA could down-regulate the expression levels of MDR1 and P-gp in K562/ADM cells. In addition, RA could upregulate the phosphorylation levels of p38 and ERK1/2 in K562/ADM cells, but it has no effect on the expression of p-JNK.
CONCLUSION:RA may participate in the regulation of MAPK signaling pathway by upregulating the expression levels of p-p38 and p-ERK1/2 in K562/ADM cells, and thus inhibit the transcription and translation levels of MDR1, and finally reverse the multidrug resistance of leukemia cells.
