Cancer is a very heterogeneous disease, in which cells at various stages of neoplasia exist within one tumour mass. Within this tumour mass are cells with varying degrees of oxygen and nutrient supply with cells in the centre of the mass being more deficient. It has been shown that tumour stem cells are to found amongst these hypoxic populations and that these cells are particularly resistant to treatment via both radiation and chemotherapy. Following treatment these resistant stem cells, form the basis of relapse or reoccurrence. These surviving cells undergo further transformation and, following relapse, are usually a more aggressive type. By utilising a hypoxic chamber, we can manipulate the oxygen supply and assess the different response of cells to tamoxifen treatment. This study assesses the impact on the breast cancer cell line, T47D, through the use of SRB, cell cycle and Annexin V/PI assays.
Results showed the cytotoxic effect of tamoxifen was enhanced when cells were exposed to both 2µM (p<0.05) and 5µM (p<0.01) tamoxifen, under hypoxic conditions. The accumulation of cells in G0/G1 phase arrest caused by tamoxifen under normoxic conditions, was not as pronounced in the hypoxic treatment. An increase in the percentage of tamoxifen treated cells undergoing apoptosis was observed when the cells were deprived of oxygen. Both 2µM (p<0.01) and 5µM (p<0.05) tamoxifen were equally potent at stimulating apoptosis in hypoxic conditions.
This study demonstrated that T47D breast cancer cells may become more responsive to the toxic effects of tamoxifen when exposed to lower levels of oxygen. This changing sensitivity of T47D breast cancer cells to tamoxifen therapy under a hypoxic environment is due to the increased accumulation of cells in G0/G1 phase, and an increase in apoptosis. However, the pathways leading to these changes and the influence of HIF survival pathways needs to be explored.