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

MARIA EVELYN CORDOBA; CUELLO-CARRIÓN, FERNANDO DARIO; MARIEL FANELLI; GISELA E. PENNACCHIO; MAGDALENA MONT-GUEVARA; MARIA LAURA VARGAS-ROIG; MARTIN GUERRERO-GIMENEZ; SILVINA NADIN

San Antonio, Texas

Congreso; San Antonio Breast Cancer Simposyum; 2018

The treatment of triple-negative breast cancers (TNBC) 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 others have 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 antineoplastic agents, such as doxorubicin. The present study sought to examine the role of the Wnt/β-catenin and HSP27 signaling pathway in response to cisplatin (CisPt)/ doxorubicin (Doxo) treatment in human triple-negative (TN) breast cancer cell lines. Material and Methods: MDA-MB231 (TN) and MCF10A cell lines were used. Cell viability was measured using MTT assay and IC50 values were obtained after 48 h of CisPt or Doxo exposition. Cellular senescence was assayed by measuring SAbeta-galactosidase (SA-beta-Gal) activity. Total and active β-catenin, HSP27, phospho HSP27, GSK3β, phospho GSK3β, p38 and phospho p38 expressions were measured by western blot and immunofluorescence. Apoptosis was measured by cleaved Caspase-3 immunofluorescence.Results: MDA-MB231 cells showed higher IC50 values for CisPt and Doxo than the MCF10A cell line. Increased numbers of senescent cells (larger and flatter) were observed in both MDA-MB231 and MCF10A cells exposed to the IC50 dose of Doxo. In MDA-MB231 cells, CisPt treatment induced caspase-3 cleavage. In MDA-MB231 cells, the expression of β-catenin, active β-catenin, total and phospho-GSK3β and total HSP27 significantly decreased in the CisPt group (p