Epithelial-mesenchymal transition (EMT) is a series of events induced in tumour cells that enable their progression from non-invasive phenotype to malignant phenotype. During EMT cancer cells lose cell-cell adhesion, epithelial characteristics and cell polarity. The biological events that occur during EMT range from activation of specific transcription factors and re-arrangement of extracellular matrix to epigenetic modifications. Epithelial-mesenchymal transition is also demonstrated to induce drug resistance to anti-cancer agents. Thus, suppressing EMT might result in inhibition of metastasis which in turn, will lead to enhanced drug response. Molecular signalling events underlying EMT and drug resistance are interrelated. Therefore, the combination of anti-cancer agents provides a stronger tool by concurrent targeting of distinct signalling pathways that regulate EMT. In the present study, Myrtucommulone-A which was previously demonstrated to suppress EMT was used in combination with cisplatin or epirubicin on breast cancer cell line MDA-MB-231. Cell migration ability was measured by wound healing assay and the alterations in EMT-related markers were detected with western blotting. While the conventional anti-cancer drugs cisplatin and epirubicin did not result in a significant change in the expressions of N-Cadherin, Vimentin and Slug, a combination of anti-cancer drugs with MC-A resulted in a decrease in EMT-related markers which was manifested as a decrease in cell migratory ability. To conclude, MC-A appears to increase anti-cancer drug response to cisplatin and epirubicin by interfering with epithelial-mesenchymal-transition and cell migration.
Anahtar Kelimeler: Epithelial-mesenchymal transition, MDA-MB-231 cells, myrtucommulone-A, cisplatin, epirubicin
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