Effect Of PI3K-AKT Signaling Pathways On Human HCT-8/FU Drug-resistant Cell P-GP Expression And Drug Resistance

ObjectiveTo study the effect of the PI3K-AKT signaling pathways on p-gp expressionand drug resistance of human colorectal carcinoma cells HCT-8/FUdrug-resistant cells in vitroMethodsMTT method was used to detect the IC50of5-Fu and resistance indexamong human colorectal carcinoma cells HCT-8cells, HCT-8/FU resistant cellsand HCT-8/FU drug-resistant cell treated with PI3K-AKT channel inhibitorsLY294002. Meanwhile, Western blot method and Cell immunohistochemicaltechnique were adopted to detect PI3K, AKT,P-AKT and P-GP expressions ofthe cell lines mentioned above.ResultThe IC50of5-Fu was (43.2±1.4)mg·L-1and (516.00±20.03)mg·L-1inthe colorectal carcinoma cells HCT-8and HCT-8/FU drug-resistant cells,respectively, with a resistance index being11.9for the latter cells；While afterHCT-8/FU drug-resistant cells were treated with drug LY294002, The IC50of5-Fu was (58.2±4.3) mg·L-1,resistance index of1.37,resulting a significantlyincreased sensitivity and a reversion index of8.8(P＜0.05)；Western blot andCell immunohistochemical technique methods test revealed that theexpressions of PI3K,Akt,P-Akt, P-GP in HCT-8/FU drug-resistant cellsincreased significantly compared to those of HCT-8cells(P＜0.05),however,they significantly declined(P＜0.05)followed by the LY294002treatment. ConclusionPI3K-Akt signaling pathways may increases the tumor cells’ drugresistance to5-FU and reduces their sensitivity to5-Fu through improving P-GPexpression.