Influence of SiRNA targeting survivin on chemosensitivity of H460/cDDP lung cancer cells

被引：35

作者：

Yang, H. ^{[1
]}

Fu, J-H ^{[1
]}

Hu, Y. ^{[1
]}

Huang, W-Z ^{[1
]}

Zheng, B. ^{[1
]}

Wang, G. ^{[1
]}

Zhang, X. ^{[1
]}

Wen, J. ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Dept Thorac Oncol, Ctr Canc, State Key Lab Oncol So China, Guangzhou 510060, Guangdong, Peoples R China

来源：

JOURNAL OF INTERNATIONAL MEDICAL RESEARCH | 2008年 / 36卷 / 04期

关键词：

lung cancer; apoptosis; survivin; drug therapy; drug resistance; chemosensitivity; RNA interference; siRNA;

D O I：

10.1177/147323000803600416

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

We investigated the difference in survivin expression between a multidrug-resistant lung cancer cell line (H460/cDDP) and its parental counterpart (H460) and the influence of siRNA targeting survivin on the chemosensitivity of H460/cDDP. SiRNA targeting survivin was transfected into H460/cDDP cells using a liposome approach. Survivin mRNA and protein expression were significantly higher in H460/cDDP than H460 cells. The median inhibitory concentrations (IC(50)s) for cisplatin and paclitaxol in vitro against H460/cDDP cells were significantly lower in cells treated with survivin-specific siRNA than in control cells. Apoptosis and cleaved caspase-3 expression were analysed using annexin V and Western blotting, respectively, and showed a significant increase in apoptosis after treatment with the chemotherapeutic agents plus specific siRNA. Specific siRNA sensitized H460/cDDP cells to both cisplatin and paclitaxol. Thus, survivin appears to participate in the multidrug resistance mechanism of H460/cDDP cells and siRNA targeting survivin has the potential to increase the sensitivity of drug-resistant cancer cells to anticancer drugs.

引用

页码：734 / 747

页数：14

共 34 条

[1] Validating survivin as a cancer therapeutic target [J].

Altieri, DC .

NATURE REVIEWS CANCER, 2003, 3 (01) :46-54

[2] A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J].

Ambrosini, G ;

Adida, C ;

Altieri, DC .

NATURE MEDICINE, 1997, 3 (08) :917-921

[3] Downregulation of Bcl-2, FLIP or IAPs (XIAP and survivin) by siRNAs sensitizes resistant melanoma cells to Apo2L/TRAIL-induced apoptosis [J].

Chawla-Sarkar, M ;

Bae, SI ;

Reu, FJ ;

Jacobs, BS ;

Lindner, DJ ;

Borden, EC .

CELL DEATH AND DIFFERENTIATION, 2004, 11 (08) :915-923

[4] Survivin gene expression in early-stage non-small cell lung cancer [J].

Falleni, M ;

Pellegrini, C ;

Marchetti, A ;

Oprandi, B ;

Buttitta, F ;

Barassi, F ;

Santambrogio, L ;

Coggi, G ;

Bosari, S .

JOURNAL OF PATHOLOGY, 2003, 200 (05) :620-626

[5]

Fink D, 1998, CLIN CANCER RES, V4, P1

[6]

Giodini A, 2002, CANCER RES, V62, P2462

[7] Transcriptional repression of the anti-apoptotic survivin gene by wild type p53 [J].

Hoffman, WH ;

Biade, S ;

Zilfou, JT ;

Chen, JD ;

Murphy, M .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (05) :3247-3257

[8]

Ikehara M, 2002, ONCOL REP, V9, P835

[9] Cancer statistics, 2006 [J].

Jemal, A ;

Siegel, R ;

Ward, E ;

Murray, T ;

Xu, JQ ;

Smigal, C ;

Thun, MJ .

CA-A CANCER JOURNAL FOR CLINICIANS, 2006, 56 (02) :106-130

[10]

Karczmarek-Borowska B, 2005, FOLIA HISTOCHEM CYTO, V43, P237

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