The Chemotherapy-sensitization Effect Of TNF-α Againat Breast Cancer Cells

Objective:The application of tumor necrosis factor-α(TNF-α) is limited by its systemic toxicity. Previous studies have shown that low-dose TNF-α sensitized cytotoxicity of chemotherapeutic agents against lung cancer, gastric cancer and hepatoma. However, evidences in breast cancer are still rare. In the present study, we investigated the therapeutic effect of TNF-α when combined with chemotherapeutics in breast cancer. This study may provide a basis for further development of TNF-α as a promising therapeutic agent for the treatment of breast cancer.Methods:1. MDA-MB-231 and MCF7 breast cancer cells were treated with different concentrations of TNF-α, docetaxel(DOC), 5-flurouracil(5-Fu), and cisplatin(DDP).2. Proliferation of breast cancer cell lines, MDA-MB-231 and MCF7, was determined by MTT(3-[4,5-dimethyltiazol-2-yl] 2,5-diphenyl-tetrazolium bromide) assay.3. Cell cycle was detected by flow cytometry analysis.4. Apoptosis was determined by flow cytometry analysis.Results:1. TNF-α promoted the proliferation of breast cancer cells.2. TNF-α significantly accelerated the cell cycle transition from G0/G1 phase to S phase.3. TNF-α significantly enhanced the cytotoxicity of docetaxel, 5-flurouracil and cisplatin against breast cancer cells.4. TNF-α promoted apoptosis induction of 5-flurouracil in breast cancer cells.Conclusion:Our present results indicated that TNF-α promoted proliferation of breast cancer cells through accelerating the cell cycle transition from G0/G1 phase to S phase, driving cell cycle out of the quiescent G0/G1 phase and the entrance into chemotherapy-sensitive proliferation cycle. TNF-α enhanced the cytotoxicity of chemotherapeutic drugs, docetaxel(DOC), 5- flurouracil(5-Fu) and cisplatin(DDP), against breast cancer cells, shedding new lights on the therapy of breast cancer.