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A New Application for the Drug Tranilast: Effects on Breast Cancer Cell Proliferation, Migration, and Invasion

˜The œFASEB journal(2010)

引用 23|浏览20
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摘要
BackgroundTranilast (Rizaben®) has been used to treat allergic and auto‐immune diseases for the last 26 years. The objective of this study was to investigate whether tranilast also has an effect on breast cancer cell biological features relevant to cancer progression, based on the its mechanism of action which involves TGFβsignaling.MethodsCultures of the BT‐474 human breast cancer cell line were used. Cell proliferation, clonogenicity, cell migration, endoglin and MMP‐9 expression were assessed by: MTT assay, soft agar colony formation, wound assay and immunocytochemistry respectively.ResultsTranilast was found to inhibit breast cancer cell proliferation by 70%. In addition, the drug decreased by 54% the number and size of cell colonies grown in soft agar, consistent with a decrease in clonogenicity. The closure of wounds made in cancer cell monolayers was slowed (55%) by Tranilast, consistent with an inhibitory effect on tumor cell migration. Endoglin, which plays a role in TGFβ signaling, was downregulated by the drug. MMP‐9, which is a metalloproteinase involved in tumor invasion and metastasis was also decreased by tranilast.ConclusionsThese results indicate that tranilast exerts inhibitory effects on key biological features of human breast cancer cells. The results are consistent with an anti‐tumor effect which can be exploited in preclinical and clinical therapeutic trials.
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