Reversal Effects Of5-Aza-2'-deoxycytidine In Combination With SAHA On Human Lung Adenocarcinoma Cisplatin-resistant Cell Line A549/DDP

Objective：To investigate the reversal effects and possible mechanism of5-Aza-2'-deoxycytidine in combination with SAHA on human lung adenocarcinoma cisplatin-resistant cell line A549/DDP．Methods：(1)MTT assay was used to screen the toxicity of5-Aza-2'-deoxycytidine andSAHA,then the non-toxic concentration(less than10percent of cell inhibition ratio),IC50of cisplatin and the resistance index were evaluated respectively；(2)Flowcytometric assay was used for measuring the effect of apoptosis；(3)The expressionlevels of resistance genes MDR1and LRP in different groups were detected byreverse transcription-polymerase chain reaction(RT-PCR)．Results：The non-toxic concentration of5-Aza-2'-deoxycytidine was5μmol/L whileSAHA was1μmol/L,they both decreased drug resistance to cisplatin in A549/DDPcells,with the reversal fold of1.6,1.8and4.6when used alone or in combination；5-Aza-2'-deoxycytidine and SAHA could decrease MDR1,LRPmRNA expressionsand induce apoptosis,the expressions and apotosis rate level in the group ofcombination with two drugs was significantly higher than those of single-treatmentgroups(all P<0.05)．Conclusion：5-Aza-2'-deoxycytidine and SAHA could partially reverse the resistance tocisplatin in A549/DDP cells,and their combination shows a synergistic effect,whichmight be related to down-regulating the expressions of MDR1and LRP genes．...