Tamoxifen in Combination Tranilast Affects Transforming Growth Factor-β Ligands and Its Receptors in MCF-7 Cells

Darakhshan, S.; Ghanbari, A.; Kakebaraei, S.; Pour, A. Bidmeshki
June 2014
Iranian Journal of Reproductive Medicine;Jun2014 Supplement, Vol. 12, p106
Academic Journal
Introduction: The transforming growth factor-β (TGF-β) signaling network plays a complex role in breast cancer. Tamoxifen is an anti-estrogen used for treatment of breast cancer. Researches show that combination of tamoxifen with other substance that helps to overcome on resistance to tamoxifen. Tranilast an anti-allergic compound that antagonizes the effects of TGF-β has been reported to reduce the metastasis of some cancers applied. Since tranilast functions through TGF-β pathway, it seems also tamoxifen affects this signaling pathway, we hypothesize that combination of these drugs may a suitable option for breast cancer treatment. Materialsand Methods: MCF-7 human breast cancer cell line were treated with different doses of tamoxifen and tranilast in combination or alone: (TAM: 1, 2, 5, 10 and 20 μM; tranilast: 10, 20, 50, 100 and 200 μM) as a single treatment and the combined treatments used were: 2 μM of tamoxifen with 5 different dose of tranilast for 48h. Proliferation inhibition was assessed by MTT assay and the effects of tranilast and/or tamoxifen on TGF-β1-3 also three surface receptors TGF-βRI-III mRNA expression using real-time RT-PCR. Inhibitory effect of these drugs on invasion and metastasis were tested by matrigel assay. Results: Tranilast and/or tamoxifen can regulate TGF-β isoforms and receptors gene expression from these cells also tranilast and/or tamoxifen inhibit migration and invasion of MCF-7 cells. Conclusion: The inhibiting expression of TGF-β contributes to the loss ability of the breast tumor cells to invade and tranilast could be a candidate drug for treatment of breast cancer patients.


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