The Reversal Effects And Mechanisms Of Juglone On Multidrug Resistance In Colon Cancer

As a common malignant tumor,colon cancer is a serious threat to human health.And it has produced resistance to a lot of clinical chemotherapy drug.Studies have confirmed that Juglone has a clear anti-tumor effect.However,there is little research about reversing resistance.In order to find an effective sensitizer to reverse the resistance of colon cancer,we investigated the effect of Juglone on the proliferation of HCT116 and HCT116/L cells in vitro,and studied the reversal effect and mechanism of Juglone on multidrug resistance of HCT116/L cells.The effect of Juglone on the proliferation of HCT116 and HCT116/L cells in vitro and the reversal of multidrug resistance in HCT116/L cells were determined by MTT assay.We used flow cytometry to determine the accumulation of rhodamine 123 in the cells and evaluated the effect of Juglone on the function of P-gp,and to measure the apoptosis rate.The mRNA expression of P-gp and bcl-2 in each group was detected by real-time fluorescent quantitative PCR.And the protein progress levels of P-gp,p-AKT,p-I?B?,I?B?,bcl-2,bax and caspase-3 were detected by ELISA.In this study,the reversal mechanism of Juglone on drug resistance in colon cancer was explored.The results showed that the HCT116 and HCT116/L cells proliferation was inhibited by Juglone after given 24 h,36 h and 48 h,and the inhibition rate increased with the increasing of concentration.In combination with oxaliplatin,the reversal multiples of were 1.57,1.66,and 1.77.Compared with HCT116/L group,the fluorescence intensity of HCT116/L+Juglone group was significantly increased(p<0.01).Compared with the positive group,the apoptosis rate of the combination group was significantly increased(p<0.01).Compared with HCT116/L group,the mRNA expression of P-gp and bcl-2 in HCT116/L+Juglone group was significantly decreased(p<0.01),the levels of P-gp and bcl-2 protein expression was decreased,AKT and I?B? phosphorylation levels was decreased,bcl-2/bax values was decreased,I?B? and caspase-3 protein expression levels was increased(p<0.05).Juglone has obvious inhibitory effect to the proliferation on HCT116 and HCT116/L cell in vitro,and has reversal effect on the multi-drug resistance of HCT116/L cells.Juglone can increase the accumulation of rhodamine 123 in HCT116/L cells and inhibit the function of P-gp.And it can sensitize HCT116/L cells to oxaliplatin,which could be by decreasing the expression of P-gp and bcl-2.The mechanism may be related to inhibition of PI3K/AKT/NF-?B pathway and activation of mitochondria-dependent caspase apoptosis pathway.