Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells

【Abstract】 Obejctive To detect the influence of antisense s oligodeoxynucleotides (S ODNs) of bd 2 and multidrug resistamce associated protein (MRP) genes multidrug resistance associated protein gene and bcl 2 antisense S oligodeoxynucleotides on cisplatin resistant lung adenocarcinoma cell line A 549 DDP which overexpresses both bcl 2 and MRP Methods A 549 DDP cells were treated with sense and antisense S ODN mediated by lipofection Expression of MRP and bcl 2 mRNA and protein in the treated cells was measured by RT PCR and flow cytometry (FCM), respectively Apoptosis was identified by DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT) mediated biotin dUTP nick end labeling(TUNEL) The degree of drug resistance of the treated cells was detected by a cell viability 3’ [4,5 dimethylthiazol 2 yl] 2,5 diphenyl tefrazolium bromide thiazolylblue (MTT) assay Results Expression of bcl 2 and MRP significantly decreased in the cells treated with bcl 2 or/and MRP antisense S ODN for 48h as compared to the cells untreated and sense treated ( P <0 05) Resistance to cisplatin in the cells treated with bcl 2 or/and MRP antisense S ODN decreased by 60 6% (6 5 times), 56 4% (7 2 times) and 71 0% (4 8 times), respectively, which paralleled the decrease of bcl 2 and MRP expression Similarly, the resistance to etoposide and epirubicin in antisense treated cells also reduced in parallel to decreases of the two gene expressions The drug resistance in sense treated cells was similar to that in untreated cells Statistically significant dose and concentration dependent increases of apoptotic cells were observed in the groups exposed to 100?μmol/L cisplatin for 48?h after treatment by bcl 2 or/and MRP antisense Conclusion Bcl 2 and MRP were at least additive and possibly synergistic in conferring drug resistance in a cisplatin resistant lung adenocarcinoma cell line Antisense S ODN could attenuate drug resistance by promoting cells apoptosis, which might lead to a new treatment for patients with non small cell lung cancers (NSCLCs) who are refractory to conventional chemotherapy更多还原