Effect Of Combining α-IFN With Thermotherapy On Reverse The Drug Resistance Of The Lung Adenocarcinoma Cell Line A549/CDDP

Objects:To investigate the effect and the possible mechanism of combination of thermotherapy andα-IFN to the drug resistance of human lung adenocarcinoma cell line A549/CDDPMethods:After being treated by CDDP(1ug/ml,2 ug/ml and 4 ug/ml),α-IFN (100U/ml,500U/ml and 1000U/ml)and thermotherapy(42℃for 2 hours),MTT method was used to detect the sensitivity of cell line A549 and A549/CDDP to CDDP. Flow cytometry detection was used to determine the expression of P-gp and the accumulation of CDDP in A549 and A549/CDDP cell line before and after the combined treatment.Results:1.The sensitivity of human lung adenocarcinoma cell line A549 andA549/CDDP to CDDP are significantly different.IC₅₀of CDDP to A549 cell line is 0.25±0.02 ug/ml and IC50 of CDDP to A549/CDDP cell line is 6.53±0.31ug/ml and RF value is 26.12,which indicated that A549/CDDP cell line is resistant to CDDP.2.α-IFN and thermotherapy have not significant inhibition to A549/CDDP cell line and the inhibition rate of them are not different(P＞0.05).3.Withα-IFN,IC50 of CDDP to A549/CDDP cell line is 2.89 ug/ml,and the inhibitiom rate of A549/CDDP cell line is significant higer than CDDP only used. There is combination effect ofα-IFN and CDDP(Q value＞1.15),which indicate thatα-IFN has sensitization effect for chemotherapy.4.Thermotherapy can reverse the drug resistance of A549/CDDP cell line.When thermotherapy in 42℃for 2 hours combined with CDDP in different concentration, the inhibition rate of A549/CDDP cell line increases significantly and different from CDDP used only(P＜0.05).5.Thermotherapy withα-IFN can further reverse the drug resistance of A549/CDDP cell line.When treated with thermotherapy andα-IFN,IC50 of CDDP to A549/CDDP cell line is 0.712 ug/ml which decreased significantly than only treated by CDDP.When treated with thermotherapy,α-IFN and CDDP,the inhibition rate of A549/CDDP cell line higher significantly than treated by CDDP andα-IFN(P＜0.05).6.P-gp expression in A549/CDDP cell line is intense and the positive rate is (91±1.4)%whereas the positive rate in A549 cell line is only(4.5±0.5)%,and the difference is significant(P＜0.05).When combined with thermotherapy andα-IFN respectively,the positive rate of P-gp expression decreased than CDDP only.When CDDP combined with thermotherapy andα-IFN,the positive rate of P-gp expression decreased further.Conclusion:1.α-IFN and thermotherapy can reverse the drug resistance of lung adenocarcinoma cell line A549/CDDP in part,and the combination ofα-IFN and thermotherapy can increase this effect.2.The effect of combination ofα-IFN and thermotherapy in reversing the drug resistance of A549/CDDP cell line may be correlated to the inhibition of P-gp expression and the increased accumulation of the chemotherapeutics inside the cells.