Effect of emodin on the improvement of drug resistance of gemcitabine in pancreatic cancer cell line by down-regulating the expression of multidrug resistance gene-1
10.13699/j.cnki.1001-6821.2018.20.010
- VernacularTitle:大黄素通过下调多药耐药基因-1的表达改善胰腺癌细胞对吉西他滨的耐药研究
- Author:
Wen-Long WANG
1
;
Qing-Zhi KONG
;
Hong-Da LU
;
Zhang LEI
;
Tao YU
;
Hong-Bin WU
;
Dian-Lei LIU
Author Information
1. 湖北中医药大学中医临床学院
- Keywords:
emodin;
gemcitabine;
pancreatic cancer;
drug resistance;
multidrug resistance gene -1
- From:
The Chinese Journal of Clinical Pharmacology
2018;34(20):2427-2430
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of emodin on the gemci-tabine-resistant pancreatic cancer cell line SW1990/Gemcitabine (GEM),and explore the potential mechanism of its action .Methods The pancreatic cancer cell line SW1990 was treated by intermittently in-creasing the concentration of gemcitabine in the culture medium for 10 months, and SW1990/GEM cells were obtained.This experiment was di-vided into control group ,emodin group,gemcitabine group and combina-tion group ( emodin +gemcitabine ) .SW1990/GEM and SW1990 cells were treated with emodin ( 10 μmol · L-1) and gemcitabine ( 20 μmol· L-1) alone or those two together in three groups for 48 h, in con-trol group cells were treated with 0.1%DMSO for 48 h.Cell proliferation was analyzed by MTT.Reverse transcription -polymerase chain reaction was performed to analyze the protein and gene expression of multidrug re-sistance gene-1 ( MDR-1) .Flow cytometric was applied to analyze the function of the P-glycoprotein(P-gp).The Rhodamine l23 efflux experiment was applied to assay P -gp function in SW1990/Gemcitabine cells.Results Compared with gemcitabine group , the combination group could significantly inhibit the proliferation of SW1990/GEM cells.Treatment of SW1990/GEM and SW1990 cells with gemcitabine alone could inhibit 13.34%and 36.52%of cell viability,there was significant difference between the two group (P＜0.05). The results showed that the SW1990 /GEM cell line had an obvious resistance to gemcitabine compared with the cell line SW 1990.While SW 1990/GEM and SW 1990 cells were treated with gemcitabine combined with emodin , cell via-bility was inhibited to 40.45%and 43.87%, there was no significant difference between the two group .The emodin could enhance the anti -proliferative effect of gemcitabine on drug -resistance cell SW1990/GEM.Compared with gemcitabine group, the combination group could significantly inhibit the expression of MDR-1 gene,and the difference was statistically significant (P＜0.05).Conclusion Effect of emodin can down -regulate the expression of MDR -1 and then improve the drug resistance of gemcitabine in pancreatic cancer .
