Department of Laboratory Medicine and Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
Exp Mol Pathol. 2011 Feb;90(1):116-22. doi: 10.1016/j.yexmp.2010.10.012. Epub 2010 Oct 30.
In the treatment of breast cancer, although a wide of choice of drugs and treatment modalities are available, drug resistance or drug toxicity poses a considerable challenge. Tranilast is a well tolerated drug used in the treatment of allergic disorders. Previous works in various models have shown that tranilast has the potential to be used as an anti-cancer drug. Hence, in this study using human breast cancer cell lines BT-474 and MDA-MB-231, we studied the effect of tranilast on cell growth, migration and ability to prevent colony formation in vitro, properties that are relevant to a possible therapeutic effect in breast cancer. We found that tranilast inhibits the growth of both breast cancer cell lines. In the cell migration experiments, the tumor cells exhibit significantly slower wound closure after tranilast treatment, as well as reduced migration using an insert system. Downregulation of MRTF-A, a global cytoskeleton regulator was observed after tranilast treatment. Additionally, tranilast treatment increased levels of cleaved PARP in both cell lines tested indicating a stimulation of apoptosis. A significant reduction in colony size and number was observed in soft agar clonogenic assays in both cell lines after tranilast treatment. BT-474 cells were more responsive to tranilast treatment compared to MDA-MB-231 cells, suggesting a difference in modes of action, or sensitivity, possibly related to their different receptor status. Based on these changes in cancer cell lines, we conclude that tranilast exerts effects that set a rationale for future preclinical studies in animal models of breast cancer.
在乳腺癌的治疗中,尽管有多种药物和治疗方式可供选择,但药物耐药性或药物毒性仍是一个相当大的挑战。曲尼司特是一种用于治疗过敏疾病的耐受性良好的药物。之前在各种模型中的研究工作表明,曲尼司特有可能被用作抗癌药物。因此,在这项使用人乳腺癌细胞系 BT-474 和 MDA-MB-231 的研究中,我们研究了曲尼司特对细胞生长、迁移和体外形成菌落能力的影响,这些特性与乳腺癌的可能治疗效果相关。我们发现曲尼司特抑制了两种乳腺癌细胞系的生长。在细胞迁移实验中,肿瘤细胞在曲尼司特处理后表现出明显较慢的伤口闭合,并且使用插入系统时迁移减少。曲尼司特处理后观察到全局细胞骨架调节剂 MRTF-A 的下调。此外,曲尼司特处理增加了两种细胞系中裂解 PARP 的水平,表明细胞凋亡受到刺激。在软琼脂集落形成实验中,两种细胞系的集落大小和数量均显著减少。BT-474 细胞对曲尼司特处理的反应性高于 MDA-MB-231 细胞,这表明作用方式或敏感性存在差异,可能与它们不同的受体状态有关。基于这些癌细胞系的变化,我们得出结论,曲尼司特发挥的作用为未来乳腺癌动物模型的临床前研究提供了依据。