Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

被引:18
作者
Hu, Li-Xia [1 ]
Du, Ying-Ying [1 ]
Zhang, Ying [2 ]
Pan, Yue-Yin [1 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Dept Oncol, Hefei, Peoples R China
[2] Anhui Med Univ, Affiliated Hosp 3, Dept Geriatr, Hefei, Peoples R China
关键词
Exemestane; aspirin; MCF-7; combination treatment; synergistic effect; CYCLOOXYGENASE-2; EXPRESSION; AROMATASE INHIBITORS; PROSTAGLANDIN E-2; COX-2; INHIBITORS; UP-REGULATION; APOPTOSIS; RISK; THERAPY; TARGET; GROWTH;
D O I
10.7314/APJCP.2012.13.11.5903
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the G(0)/G(1) phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone-dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.
引用
收藏
页码:5903 / 5908
页数:6
相关论文
共 52 条
[1]  
Abbadessa G, 2006, INT J ONCOL, V28, P1131
[2]   A novel role for cyclooxygenase-2 in regulating vascular channel formation by human breast cancer cells [J].
Basu, Gargi D. ;
Liang, Winnie S. ;
Stephan, Dietrich A. ;
Wegener, Lee T. ;
Conley, Christopher R. ;
Pockaj, Barbara A. ;
Mukherjee, Pinku .
BREAST CANCER RESEARCH, 2006, 8 (06)
[3]   Aspirin and the risk of colorectal cancer in relation to the expression of COX-2 [J].
Chan, Andrew T. ;
Ogino, Shuji ;
Fuchs, Charles S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (21) :2131-2142
[4]   QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].
CHOU, TC ;
TALALAY, P .
ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55
[5]  
Chulada PC, 2000, CANCER RES, V60, P4705
[6]   Cyclo-oxygenase inhibition reduces tumour growth and metastasis in an orthotopic model of breast cancer [J].
Connolly, EM ;
Harmey, JH ;
O'Grady, T ;
Foley, D ;
Roche-Nagle, G ;
Kay, E ;
Bouchier-Hayes, DJ .
BRITISH JOURNAL OF CANCER, 2002, 87 (02) :231-237
[7]   Cyclooxygenase-1 is overexpressed in multiple genetically engineered mouse models of epithelial ovarian cancer [J].
Daikoku, T ;
Tranguch, S ;
Trofimova, IN ;
Dinulescu, DM ;
Jacks, T ;
Nikitin, AY ;
Connony, DC ;
Dey, SK .
CANCER RESEARCH, 2006, 66 (05) :2527-2531
[8]   Cyclooxygenase-1 is a potential target for prevention and treatment of ovarian epithelial cancer [J].
Daikoku, T ;
Wang, DZ ;
Tranguch, S ;
Morrow, JD ;
Orsulic, S ;
DuBois, RN ;
Dey, SK .
CANCER RESEARCH, 2005, 65 (09) :3735-3744
[9]   Extracellular signal-regulated kinase is a target of cyclooxygenase-1-peroxisome proliferator-activated receptor-δ signaling in epithelial ovarian cancer [J].
Daikoku, Takiko ;
Tranguch, Susanne ;
Chakrabarty, Anindita ;
Wang, Dingzhi ;
Khabele, Dineo ;
Orsulic, Sandra ;
Morrow, Jason D. ;
DuBois, Raymond N. ;
Dey, Sudhansu K. .
CANCER RESEARCH, 2007, 67 (11) :5285-5292
[10]   Cyclooxygenase-2 (COX-2), aromatase and breast cancer: a possible role for COX-2 inhibitors in breast cancer chemoprevention [J].
Davies, G ;
Martin, LA ;
Sacks, N ;
Dowsett, M .
ANNALS OF ONCOLOGY, 2002, 13 (05) :669-678