| Yin Lina,Zhang Xuxia,Wang Jing,Zhang Yaping,Bao Yizhong,Zhang Junxiang,Chen Honghong.Radiosensitization of human triple-negative breast cancer MDA-MB-231 cells by antihelminthic niclosamide[J].Chinese Journal of Radiological Medicine and Protection,2014,34(4):244-249 |
| Radiosensitization of human triple-negative breast cancer MDA-MB-231 cells by antihelminthic niclosamide |
| Received:August 27, 2013 |
| DOI：10.3760/cma.j.issn.0254-5098.2014.04.002 |
| KeyWords:Niclosamide Radiosensitization β-catenin MDA-MB-231 cells |
| FundProject:上海市自然科学基金（13ZR1403500） |
| Author Name | Affiliation | E-mail | | Yin Lina | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Zhang Xuxia | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Wang Jing | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Zhang Yaping | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Bao Yizhong | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Zhang Junxiang | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | | | Chen Honghong | Department of Radiation Biology, Institute of Radiation Medicine, Fudan University, Shanghai 200032, China | hhchen@shmu.edu.cn |
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| Abstract:: |
| Objective To investigate the radiosensitization effect of antihelminthic niclosamide on human triple-negative breast cancer MDA-MB-231 cells and the potential mechanism related to Wnt/β-catenin signaling pathway. Methods Four methyl thiazolyl tetrazolium(MTT)assay was used to measure the effect of niclosamide on cell viability at different concentrations and 50% inhibitory concentration(IC50)value was calculated. MDA-MB-231 cells were divided into 4 groups: untreated control, niclosamide treatment alone group, radiation alone group and niclosamide plus radiation treatment group. The cells with or without 1.0 and 1.5 μmol/L niclosamide pre-treatment were irradiated with 137Cs γ-rays at doses of 0, 2, 4 and 6 Gy. Cell survival was assayed with the colony formation method, radiation-induced γH2AX foci was analyzed with immunofluorescence, cell cycle progression was assayed with flow cytometry, and the changes of phospho-and non-phospho-β-catenin and Cyclin D1 protein expressions were measured with Western blot. Results Niclosamde obviously inhibited the viability of MDA-MB-231 cells in a dose-dependent manner with a IC50 value of 13.63 μmol/L. Pretreatment of cells with 1.0 and 1.5 μmol/L niclosamide evidently enhanced the radiosensitivity of MDA-MB-231 cells to γ-rays, and the values of SER were 1.37 and 1.62, respectively. Niclosamide pretreatment significantly increased radiation-induced γH2AX foci formation(t=3.91, P<0.05), diminished the radiation-induced G2/M arrest(t=8.05, P<0.01), and inhibited radiation-induced expressions of phospho-β-catenin (S675),non-phospho-β-catenin and Cyclin D1 proteins in MDA-MB-231 cells. Conclusions Niclosamide significantly can enhance the sensitivity of MDA-MB-231 cells to γ-ray irradiation through inhibiting Wnt/β-catenin signaling pathway, which results in the inhibition of DNA DSBs repair and the reduction of radiation-induced G2/M arrest. Wnt/β-catenin signaling pathway may serve as an ideal molecular target for radiosensitization of triple-negative breast cancer. |
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