Inhibition of Survivin Restores the Sensitivity of Breast Cancer Cells to Docetaxel and Vinblastine

被引:43
作者
Ghanbari, Parisa [1 ,2 ]
Mohseni, Mahsa [1 ,2 ]
Tabasinezhad, Maryam [1 ,2 ]
Yousefi, Bahman [3 ]
Saei, Amir Ata [2 ]
Sharifi, Simin [2 ]
Rashidi, Mohammad Reza [2 ]
Samadi, Nasser [1 ,2 ,3 ]
机构
[1] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Biotechnol, Tabriz, Iran
[2] Tabriz Univ Med Sci, Res Ctr Pharmaceut Nanotechnol, Tabriz, Iran
[3] Tabriz Univ Med Sci, Fac Med, Dept Biochem & Clin Labs, Tabriz, Iran
关键词
Chemoresistance; Deguelin; Docetaxel; MDA-MB-231; Vinblastine; PROSTATE-CANCER; LUNG-CANCER; HEPATOCELLULAR-CARCINOMA; PROGNOSTIC PARAMETERS; MICROTUBULE DYNAMICS; APOPTOSIS PROTEINS; DOWN-REGULATION; OVARIAN-CANCER; EXPRESSION; RESISTANCE;
D O I
10.1007/s12010-014-1125-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Combination therapy is considered a viable strategy to overcome the resistance to chemotherapeutics. Survivin as a member of the inhibitor of apoptosis protein (IAP) family, which is involved in resistance to various drugs. We investigated the role of combination therapy in downregulating survivin and increasing drug's efficacy in MDA-MB-231 cells. MTT assay and DAPI staining were applied to study the anti-proliferative activity and apoptosis response of the agents. Real-time RT-PCR and Western blot analysis were applied to study survivin mRNA and protein. Our findings showed that combined treatment of cells with docetaxel and vinblastine reduces survivin expression and consequently decreases the IC50 value of docetaxel from 70 to 5 nM (p < 0.05). Furthermore, combination therapy with deguelin, a survivin inhibitor, exerted a considerable enhancement in synergistic efficacy of docetaxel and vinblastine (p < 0.05). Survivin downregulation may thus be considered a potential strategy in increasing the efficacy of chemotherapeutics in cancer patients.
引用
收藏
页码:667 / 681
页数:15
相关论文
共 64 条
[1]   The case for survivin as a regulator of microtubule dynamics and cell-death decisions [J].
Altieri, Dario C. .
CURRENT OPINION IN CELL BIOLOGY, 2006, 18 (06) :609-615
[2]  
Aoudjit Fawzi, 2012, Chemother Res Pract, V2012, P283181, DOI 10.1155/2012/283181
[3]   3,3′-Diindolylmethane Enhances the Efficacy of Butyrate in Colon Cancer Prevention through Down-Regulation of Survivin [J].
Bhatnagar, Namrata ;
Li, Xia ;
Chen, Yue ;
Zhou, Xudong ;
Garrett, Scott H. ;
Guo, Bin .
CANCER PREVENTION RESEARCH, 2009, 2 (06) :581-589
[4]  
Blanc-Brude OP, 2003, CLIN CANCER RES, V9, P2683
[5]   Survivin is required for stable checkpoint activation in taxol-treated HeLa cells [J].
Carvalho, A ;
Carmena, M ;
Sambade, C ;
Earnshaw, WC ;
Wheatley, SP .
JOURNAL OF CELL SCIENCE, 2003, 116 (14) :2987-2998
[6]   Role of X-linked inhibitor of apoptosis protein in chemoresistance in ovarian cancer: possible involvement of the phosphoinositide-3 kinase/Akt pathway [J].
Cheng, JQ ;
Jiang, XX ;
Fraser, M ;
Li, M ;
Dan, HC ;
Sun, M ;
Tsang, BK .
DRUG RESISTANCE UPDATES, 2002, 5 (3-4) :131-146
[7]   Chemotherapy for metastatic breast cancer -: report of a European expert panel [J].
Crown, J ;
Diéras, V ;
Kaufmann, M ;
von Minckwitz, G ;
Kaye, S ;
Leonard, R ;
Marty, M ;
Misset, JL ;
Osterwalder, B ;
Piccart, M .
LANCET ONCOLOGY, 2002, 3 (12) :719-727
[8]   Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis [J].
Dohi, T ;
Beltrami, E ;
Wall, NR ;
Plescia, J ;
Altieri, DC .
JOURNAL OF CLINICAL INVESTIGATION, 2004, 114 (08) :1117-1127
[9]  
Drukman S, 2002, INT J ONCOL, V21, P621
[10]   Survivin: A promising tumor biomarker [J].
Duffy, Michael J. ;
O'Donovan, Norma ;
Brennan, Donal J. ;
Gallagher, William M. ;
Ryan, Brid M. .
CANCER LETTERS, 2007, 249 (01) :49-60