|Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells|
|Wang, J; Liu, XY; Jiang, W|
|关键词||a(549) And a(549)(Ddp) Cell Lines Drug Resistance Apoptosis Lung Neoplasms Antisense S-oligodeoxynucleotide|
|刊名||CHINESE MEDICAL JOURNAL|
|WOS标题词||Science & Technology|
|类目[WOS]||Medicine, General & Internal|
|研究领域[WOS]||General & Internal Medicine|
|关键词[WOS]||PROTEIN MRP ; OLIGONUCLEOTIDES ; INHIBITION ; EXPRESSION ; APOPTOSIS|
Objective To detect the influence of antisense s-oligodeoxynucleotides (S-ODNs) of bd-2 and multidrug resistance-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 A549DDP 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 mu mol/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.
|作者单位||Beijing Med Univ, Sch Oncol, Dept Internal Med, Beijing 100036, Peoples R China|
|Wang, J,Liu, XY,Jiang, W. Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells[J]. CHINESE MEDICAL JOURNAL,2000,113(10):957-960.|
|APA||Wang, J,Liu, XY,&Jiang, W.(2000).Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells.CHINESE MEDICAL JOURNAL,113(10),957-960.|
|MLA||Wang, J,et al."Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells".CHINESE MEDICAL JOURNAL 113.10(2000):957-960.|
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