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学科主题: 临床医学
题名:
Co-transfection of MRP and bcl-2 antisense S-oligodeoxynucleotides reduces drug resistance in cisplatin-resistant lung cancer cells
作者: 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
发表日期: 2000-10-01
卷: 113, 期:10, 页:957-960
收录类别: SCI
文章类型: Article
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
英文摘要:

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.

语种: 英语
WOS记录号: WOS:000089840800020
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52198
Appears in Collections:北京大学临床肿瘤学院_期刊论文

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作者单位: Beijing Med Univ, Sch Oncol, Dept Internal Med, Beijing 100036, Peoples R China

Recommended Citation:
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.
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