Radiation responses of chemoresistant adenocarcinoma cells : from molecular mechanisms to new reversal strategies

Abstract

Breast cancer is a major cause of cancer-related death among women throughout the world. Treatment of breast cancer often fails due to the development of resistance to both chemo- and radiotherapy. The aim of this study was to analyze and compare the response to radiation of MCF-7 breast adenocarcinoma cells and MCF-7 cells that are resistant to doxorubicin (MCF-7/DOX). The results presented in this thesis show that drug-resistant MCF-7/DOX cells survive high doses of radiation exposure better than MCF-7 cells. Moreover, the chemo- and radioresistance of MCF-7/DOX cells share common molecular mechanisms and loss of sensitivity to radiation in chemo-resistant cells may be explained by alterations in their DNA methylation profile. The results of experiments presented in this thesis may, therefore, serve as a first step for future analysis of tumour resistance to radio- and chemotherapy and for the development of novel epigenetic strategies for reversal of breast cancer resistance to cytotoxic treatment regimens.