Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells
Effectiveness of sulforaphane as a radiosensitizer for murine osteosarcoma cells
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DOI：
10.3892/or.2012.2195
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发表时间：
2013-03-01
期刊：
影响因子：
4.2
通讯作者：
Fushiki, Shinji
中科院分区：
文献类型：
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作者：
Sawai, Yasushi;Murata, Hiroaki;Fushiki, Shinji
萝卜硫素（SFN）是异硫氰酸酯家族的天然成员，对各种类型的恶性肿瘤细胞有效。我们研究了SFN和辐射的组合是否比单独使用这些治疗方法更有效地对抗骨肉瘤细胞。将LM 8鼠骨肉瘤细胞与不同浓度的SFN一起培养24小时和/或2戈伊X射线照射。分析单药及联合用药对细胞数量、细胞周期、细胞增殖相关因子及细胞凋亡的影响。SFN加放疗的联合治疗比单独治疗具有更大的抗肿瘤作用。暴露于SFN增加了处于G（2）/M期的细胞群体。联合治疗导致亚G细胞的百分比高于SFN单独治疗。此外，SFN和辐射的组合有效地诱导核碎裂和凋亡小体，如DAPI染色所示。Western印迹显示，与SFN或单独辐射相比，SFN和2戈伊辐射的组合增加了caspase-3的切割和活化。虽然单独辐射增加ERK和Akt蛋白的磷酸化，SFN和辐射的组合诱导ERR和Akt磷酸化的抑制相比，单独辐射。我们发现，SFN通过诱导细胞凋亡（通过G（2）/M期阻滞）和抑制ERK和Akt激活，增强了LM 8小鼠骨肉瘤细胞的放射敏感性。这些结果表明，SFN可作为骨肉瘤的放射增敏剂。
Sulforaphane (SFN), a naturally occurring member of the isothiocyanate family, is effective against various types of malignant tumor cells. We studied whether the combination of SFN and radiation would be more effective against osteosarcoma cells when compared to these treatments alone. LM8 murine osteosarcoma cells were cultured with various concentrations of SFN for 24 h and/or 2 Gy X-irradiation. The effects of individual and combination treatments on the number of cells, the cell cycle, cell proliferation-related factors and apoptosis were analyzed. The combination of SFN plus radiation had significantly greater antitumor effects than either treatment alone. Exposure to SFN increased the population of cells in the G(2)/M phase. Combination treatment resulted in a higher percentage of cells being in sub-G, than did SFN alone. In addition, the combination of SFN and radiation effectively induced nuclear fragmentation and apoptotic bodies, as shown by DAPI staining. The combination of SFN and 2 Gy radiation increased the cleavage and activation of caspase-3 compared with SFN or radiation alone, as shown by western blotting. Although radiation alone increased the phosphorylation of ERK and Akt proteins, the combination of SFN and radiation induced suppression of ERR and Akt phosphorylation when compared with radiation alone. We found that SFN enhanced the radiosensitivity of LM8 murine osteosarcoma cells by inducing apoptosis through G(2)/M-phase arrest and by inhibiting ERK and Akt activation. These findings suggest that SFN can be used as a radiosensitizer for osteosarcomas.