Involvement of p53 in gemcitabine mediated cytotoxicity and radiosensitivity in breast cancer cell lines.

Abstract Gemcitabine (2′,2′-difluoro-2′-deoxycytidine; dFdCyd) is one of the anti-metabolites drugs that target DNA replication. We evaluated dFdCyd cytotoxicity and its radiosensitizing ability in human breast cancer cell lines, MCF-7 (wild-type p53) and MDA-MB-231 (mutant-type p53) along with normal mammary epithelial cell line (MCF-12) for comparison. Radiosensitivity and cytotoxicity were measured by the clonogenic survival assays. DNA DSBs was studied by Pulse Field Gel Electrophoresis (PFGE) and cell cycle distribution was analyzed by flow cytometry. MDA-MB-231 cells were the most sensitive to the cytotoxicity of dFdCyd (IC 50 5 nM) then MCF-7 (IC 50 10 nM), whereas MCF-12 cells were the most resistant to the cytotoxicity of dFdCyd (IC 50 70 nM). MCF-12 and MCF-7 cell lines did not show any radiosensitization to dFdCyd, whereas the MDA-MB-231 cells showed significantly increased radioresistant to dFdCyd at equimolar concentration (p = 0.002) and at IC 50 concentration (p