دراسة العلاقة بين مقاومة الخلايا MDA-MB-231 لمركب السيسبلاتين و التحول الظهاري الميزانشيمي

Abstract EN

Breast cancer is the main cause of death in women worldwide.

Breast cancer is heterogeneous at the molecular level and in their response to chemotherapy.

Chemoresistant is an essential reason for treatment failure and the high mortality.

Emerging evidence associates Epithelial-to-mesenchymal transition (EMT) and acquisition of chemoresistance in cancer.

Here we investigate the response of MDA-MB-231 and MCF7 cell lines to cisplatin and we determine the epithelial/ mesenchymal status of these cells at the morphological and molecular level.

MDA-MB-231 and MCF7 cells were treated with increased concentrations of cisplatin.

Cell viability and resistance fold change were determined by XTT.

The EMT features were studied at morphological and molecular levels under microscope and mRNA expression studying.

Snail/E-cadherin index was determined to compare and identify the epithelial/mesenchymal status of the studied cell lines.

Our results indicated that cisplatin treatment reduced the cell viability for both studied cell lines.

MDA-MB-231 cells were more resistant to cisplatin than MCF7 cells.

The spindle-like morphology was documented for MDA-MB-231 cells using light microscope, and the value of the Snail /E-cadherin index for MDA-MB-231 cells was 5.2 compared to MCF7 cells.

The expression of E-cadherin and EPCAM genes that regulate epithelial status were decreased.

These decreases were associated with upregulation of EMT- genes such as SNAIL, ZEB1 and TWIST2.

We conclude that the resistance of MDA-MB-231 cell line to cisplatin is associated with a mesenchymal like cellular status, so targeting EMT genes may be a novel approach that reverses chemoresistance and increases the effectiveness of chemotherapy.