Epithelial-mesenchymal transition as a potential route for DAPT resistance in breast cancer cells

نویسندگان

چکیده

Abstract Objectives Notch is a conserved pathway involved in cell-fate determination and homeostasis. Its dysregulation plays role poor prognosis drug resistance breast cancer. Targeting signaling via inhibition of the gamma-secretase complex spotlight modern cancer treatments. Gamma-secretase inhibitors (GSI) have shown successful clinical activity treating cancers, yet possible mechanism remains unstudied. Modeling understanding culprit molecular mechanisms can improve GSI therapies. Accordingly, aim this study to generate analyze GSI-resistant cells. Methods Gradually increasing doses DAPT, well-known GSI, were applied MCF-7 cell lines resistance. Cell viability, migration gene expressions assessed by MTT, wound healing qRT-PCR analyses. Results DAPT-resistant cells exhibited abnormal expression receptors, targets (HES1, HES5, HEY1), epithelial-mesenchymal transition (EMT) markers (E-cadherin, ZO-1, SNAIL2, N-cadherin) overcome continuous increase DAPT toxicity increased through mesenchymal transition. Conclusions This prospects into EMT potential against treatment for Complementary targeting should be investigated further effect potentiate DAPT’s anti-cancer effects.

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ژورنال

عنوان ژورنال: Türk biyokimya dergisi

سال: 2023

ISSN: ['1303-829X']

DOI: https://doi.org/10.1515/tjb-2022-0218