Synergistic Effects of Tamoxifen and Tranilast on VEGF and MMP-9 Regulation in Cultured Human Breast Cancer Cells

被引:20
作者
Darakhshan, Sara [1 ]
Bidmeshkipour, Ali [1 ]
Khazaei, Mozafar [2 ]
Rabzia, Arezou [2 ]
Ghanbari, Ali [2 ]
机构
[1] Razi Univ, Fac Sci, Dept Biol, Kermanshah, Iran
[2] Kermanshah Univ Med Sci, Fertil & Infertil Res Ctr, Kermanshah, Iran
关键词
Breast cancer; tamoxifen; tranilast; angiogenesis; matrix metalloproteinase; ENDOTHELIAL GROWTH-FACTOR; MATRIX METALLOPROTEINASES; ESTROGEN-RECEPTOR; ESTRADIOL; ANGIOGENESIS; METASTASIS; EXPRESSION; PROLIFERATION; MIGRATION; TARGET;
D O I
10.7314/APJCP.2013.14.11.6869
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.
引用
收藏
页码:6869 / 6874
页数:6
相关论文
共 40 条
[1]   Differential influence of antiestrogens on the in vitro release of gelatinases (type IV collagenases) by invasive and non-invasive breast cancer cells [J].
Abidi, SMA ;
Howard, EW ;
Dmytryk, JJ ;
Pento, JT .
CLINICAL & EXPERIMENTAL METASTASIS, 1997, 15 (04) :432-439
[2]   Critical Role of Hypoxia Sensor - HIF-1α in VEGF Gene Activation. Implications for Angiogenesis and Tissue Injury Healing [J].
Ahluwalia, A. ;
Tarnawski, A. S. .
CURRENT MEDICINAL CHEMISTRY, 2012, 19 (01) :90-97
[3]  
Applanat MP, 2008, ADV EXP MED BIOL, V617, P437, DOI 10.1007/978-0-387-69080-3_42
[4]   PHARMACOLOGICAL PROPERTIES OF N-(3',4'-DIMETHOXYCINNAMOYL) ANTHRANILIC ACID (N-5'), A NEW ANTI-ATOPIC AGENT [J].
AZUMA, H ;
BANNO, K ;
YOSHIMURA, T .
BRITISH JOURNAL OF PHARMACOLOGY, 1976, 58 (04) :483-488
[5]   Mechanisms of Disease: angiogenesis and the management of breast cancer [J].
Banerjee, Susana ;
Dowsett, Mitch ;
Ashworth, Alan ;
Martin, Lesley-Ann .
NATURE CLINICAL PRACTICE ONCOLOGY, 2007, 4 (09) :536-550
[6]   Tumorigenesis and the angiogenic switch [J].
Bergers, G ;
Benjamin, LE .
NATURE REVIEWS CANCER, 2003, 3 (06) :401-410
[7]   Tranilast inhibits the growth and metastasis of mammary carcinoma [J].
Chakrabarti, Rabindranath ;
Subramaniam, Venkateswaran ;
Abdalla, Salma ;
Jothy, Serge ;
Prud'homme, Gerald J. .
ANTI-CANCER DRUGS, 2009, 20 (05) :334-345
[8]   NEW ANTI-OESTROGENIC AGENT IN LATE BREAST CANCER - EARLY CLINICAL APPRAISAL OF ICI46474 [J].
COLE, MP ;
JONES, CTA ;
TODD, IDH .
BRITISH JOURNAL OF CANCER, 1971, 25 (02) :270-&
[9]   Estradiol increases extracellular levels of vascular endothelial growth factor in vivo in murine mammary cancer [J].
Dabrosin, C ;
Margetts, PJ ;
Gauldie, J .
INTERNATIONAL JOURNAL OF CANCER, 2003, 107 (04) :535-540
[10]   The biology of VEGF and its receptors [J].
Ferrara, N ;
Gerber, HP ;
LeCouter, J .
NATURE MEDICINE, 2003, 9 (06) :669-676