DIFFERENTIAL EXPRESSION AND LOCALIZATION OF BETA-CATENIN AND HSP27 AFTER CISPLATIN/DOXORUBICIN TREATMENT IN TRIPLE NEGATIVE BREAST CANCER CELLS

MARIA EVELYN CÓRDOBA; CUELLO CARRIÓN, FERNANDO DARÍO; FANELLI MARIEL; NIUBYS CAYADO-GUTIÉRREZ; LAURA M. VARGAS-ROIG; GISELA PENNACCHIO; SILVINA NADIN

San Luis

Congreso; XXXVII Reunión Científica Anual Sociedad de Biología de Cuyo; 2019

The treatment of triple-negative breast cancers involves the administration of the conventional chemotherapeutic drug doxorubicin,given the lack of specific targeted agents. Novel therapeutic strategies, such as cisplatin, are currently being tested for these patients.Many studies have demonstrated that aberrant Wnt/β-catenin signaling serves a role in the development of breast cancer, while othershave concluded that abnormal regulation of Wnt pathway induces tumor cell chemoresistance. The small heat shock protein 27 (HSP27) is overexpressed in human breast cancer cells. As a result, cancer cells may suppress apoptosis and develop resistance to antineoplasticagents, such as doxorubicin. The present study sought to examine the role of the Wnt/β-catenin and HSP27 signaling pathway inresponse to cisplatin (CisPt)/doxorubicin (Doxo) treatment in human triple-negative (TN) breast cancer cell lines. Material andMethods: MDA-MB231 (TN) and MCF10A cell lines were used. Cell viability was measured using MTT assay and IC50 values wereobtained after 48 h of CisPt or Doxo exposition. β-catenin and Hsp27 gene expression were measured by qPCR. Total and active βcatenin, phosphor ant total HSP27, phospho and GSK3β, phosphor and total p38 expressions were measured by western blot andimmunofluorescence. 3D cell culture from MDA MB231 cells were treated with increasing concentrations of CisPt and Doxo for 48h.Results: MDA-MB231 cells showed higher IC50 values for CisPt and Doxo than the MCF10A cell line. In MDA-MB231 cells, theexpression of β-catenin, active β-catenin, total and phospho-GSK3β and total HSP27 significantly decreased in the CisPt group(p