PO-125 Role of NRF2 in breast cancer stem cells resistance and tumourrecurrence

Abstract

correspondingly. MiR-1246 modified the influence of P53 to mTOR, which indicated its effect in the mediating DNA damage repair and autophagy. Conclusion MiR-1246 decreased the sensitivity of lung cancer cells to radiation through activation of autophagy by targeting mTOR. It was also been demonstrated the significant crosstalk between DNA damage repair and the ups in autophagy. This special mechanism made miR-1246 a potential therapeutic target to overcome the resistance to radiation in non-small cell lung cancer patients. Introduction Advancements in radio/chemo therapies have significantly decreased the mortality rate in breast cancer patients; however, resistance and recurrence of the tumour are major concerns with these therapies. Recurrence after radiation therapy is initiated by a subpopulation that is highly radio resistant, known as cancer stem cells (CSCs). One of the main ways of radio therapy to kill cancer cells is by increasing the cellular oxidative stress. Due to higher metabolic and proliferative rate, cancer cells become well-adapted to intrinsic oxidative stress. CSCs are quiescent and work under low levels of oxidative stress It is assumed that CSCs escape radio therapy by modulating redox homeostasis. Nrf2 pathway is a central cellular pathway that protects against oxidative stress. Nrf2 plays a dual role in cancer protection as well as cancer progression by up-regulating the expression of cytoprotective genes and reducing oxidative stress. In our study, we hypothesised that Nrf2 signalling pathway might be involved in radio resistance and low ROS levels in Breast CSCs (BCSCs). Material and methods MCF-7 and MDA-MB-231 cell lines were used for CSC isolation and CSCs were characterised by CD44 + /CD24 -/ESA + , ALDH + activity. BCSCs were irradiated with fractionated dose of g-radiation. Protein and mRNA levels were analysed by western blotting and real time-PCR respectively. Radio resistance was checked by colony formation assays. We examined the ROS levels in BCSCs and non-BCSCs after fractionated irradiation. ROS levels were found to be decreased in BCSCs as compare to nonBCSCs after fractionated dose irradiation. We checked the radio-resistance in irradiated cells via radio-resistance assay. More numbers of radio-resistant colonies were formed in the fractionated dose irradiated BCSCs than non-BCSCs. Expression levels of Nrf2 and its downstream regulators were checked in fractionated dose irradiation and were found to be elevated in BCSCs irradiated with fractionated dose than nonBCSCs. Conclusion BCSCs have low levels of ROS and high levels of antioxidants which may contribute to the radio-resistance of BCSCs. Elucidation of role of Nrf2 in BCSCs resistance and tumour recurrence may provide an effective strategy to overcome radio-resistance. PO-125 ROLE OF NRF2 IN BREAST CANCER STEM CELLS RESISTANCE AND TUMOURRECURRENCE Results and discussions