A23187 May Improve Tamoxifen Sensitivity of Tamoxifen-Resistant Breast Cancer Cells

Abstract

Objective: Tamoxifen is the most widely used therapeutic agent for the treatment of ER α-positive breast cancer. However, the development of resistance to tamoxifen in the majority of patients limits the therapeutic efficacy of tamoxifen and reduces the survival rate of patients. Ca+2 signaling mechanism, which has many critical roles including cell motility and gene expression regulation, has important roles in processes such as proliferation, migration, angiogenesis, and drug resistance development related to carcinogenesis. In this study, we aimed to investigate the effect of Calcium ionophore A23187 (calcimicin), which has high Ca+2 selectivity and mediates Ca+2 output from the endoplasmic reticulum, on proliferation and tamoxifen resistance in tamoxifen-resistant breast cancer cells. Materials and Methods: WST-1-based cell proliferation analyzes were performed to evaluate the effect of A23187 or Tamoxifen and A23187 combined treatment on cell proliferation in Tamoxifen-resistant breast cancer cells MCF-7/TAMR-1. In addition, microscopic examinations were performed and photographed. Results: A21387 has an antiproliferative effect on MCF-7/TAMR-1 cells. Moreover, a combined treatment of A23187 and tamoxifen synergistically reduced the proliferative capacity of cells manner dose-dependent by limiting tamoxifen resistance. Conclusion: Our findings suggest that modulation of calcium signaling by A23187 may be a promising approach to improve tamoxifen sensitivity in breast cancer cells.