Development of radioresistance in drug resistant human MCF-7 breast cancer cells

Abstract

Background and purpose: Radiotherapy is used for the treatment of malignant tumours, and may be used as the primary therapy. It is also common to combine radiotherapy with surgery, chemotherapy, hormone therapy or some combination of them. Even if the tumour is treated intensively, women diagnosed with breast cancer may develop a recurrence. Most recurrences may be in the form of distant metastases, development of multi-drug resistance phenotype or both together. This study demonstrated that some of the multi-drug resistant cancer cells may also become radioresistant.Materials and Methods: Chemoresistance in paclitaxel (MCF-7/Pac), docetaxel (MCF-7/Doc), vincristine (MCF-7/Vinc), doxorubicin (MCF-7/Dox) and zoledronic acid (MCF-7/Zol) resistant MCF-7 cells were demonstrated by XTT assay. MDR1 gene expression was detected by real-time PCR in human MCF-7 breast cancer cells. Drug resistant and sensitive cells were exposed to γ-radiation and development of radioresistance was investigated.Results: Results have indicated that paclitaxel, docetaxel, vincristine, doxorubicin and zoledronic acid–selected cells gained varying degrees of resistance to their selective drugs when compared with original MCF-7/S. MCF-7/Pac, MCF-7/Doc, MCF-7/Vinc and MCF-7/Dox cells have all acquired MDR1 expression. Among the resistant sub-lines, MCF-7/Pac and MCF-7/Doc cells were significantly cross-resistant to irradiation compared to the sensitive cells.Conclusion: MCF-7/Pac and MCF-7/Doc cell lines were found radioresistant to γ-radiation. On the contrary, doxorubicin, vincristine and zoledronic acid resistant cancer cells were still sensitive to radiation.