Reversal Effects of Curcumin on Gemcitabine-resistant Pancreatic Cancer SW 1990 Cells and Its Mechanism Study / 中国药房

ABSTRACT

OBJECTIVE： To study the effects of curcumin on gemcitabine （GEM）-resistant pancreatic cancer SW1990 cells and its mechanism. METHODS： CCK8 assay was used to detect the effects of different concentrations of GEM （50， 100， 150， 200， 250 μmol/L） on the survival rate of SW1990 cells and GEM-resistant SW1990 cells （SW1991/GEM resistant cells）； half inhibitory concentration （IC50） and drug resistance multiple were calculated. CCK8 assay was performed to detect the effects of different concentrations of curcumin （1， 5， 10， 20， 40 μmol/L） on survival rate of SW1990/GEM resistant cells， and IC50 was calculated. CCK8 assay was used to detect the effects of curcumin 2.41 μmol/L combined with different concentrations of GEM （25， 50， 75， 100， 125 μmol/L） on the survival rate of SW1990 cells and SW1990/GEM resistant cells， and IC50 and drug resistance reversal fold of GEM were calculated. Flow cytometry was carried out to detect the cell cycle distribution and apoptosis rate of SW1990 after treated with GEM alone or curcumin （2.41 μmol/L） combined with GEM using IC50 of GEM as drug concentration. Western blot assay was used to the protein expression of FAS， AKT， p-AKT， PI3K， p-PI3K， Caspase-3， Bcl-2 and related X protein （Bax）. RT-PCR was used to detect mRNA expression. RESULTS： IC50 of GEM to SW1990 cells was 92 μmol/L. IC50 of GEM to SW1990/GEM resistant cells was 216 μmol/L， and drug resistance multiple SW1990 cells to GEM was 2.35. IC50 of curcumin to SW1990/GEM resistant cells was 9.2 μmol/L. Under 2.41 μmol/L curcumin， IC50 of GEM to SW1990 cells was 75  μmol/L， and IC50 of GEM to SW1990/GEM resistant cells was 98 μmol/L； drug resistance reversal multiple of SW1990/GEM resistant cells to GEM was 2.2. Compared with GEM alone， the apoptosis rate of SW1990 cells and SW1990/GEM resistant cells were increased significantly after curcumin combined with GEM （P＜0.05）， blocking at G0/G1 phase； the protein expression of FAS， p-AKT， p-PI3K and Bcl-2 and mRNA expression of FAS and Bcl-2 were decreased significantly  （P＜0.05）； the protein and mRNA expression of Bax      and Caspase-3 were increased significantly （P＜0.05）. CONCLUSIONS： Curcumin can reverse drug resistance of SW1990 cells to GEM， the mechanism of which may be associated with PI3K/AKT pathway.