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目的:研究叶酸修饰稀土改性载氧碳纳米管在低氧环境下对乳腺癌细胞株放疗敏感性的影响。方法:使用水溶性四唑盐法(WST-1)方法研究叶酸修饰稀土改性载氧碳纳米管对MDA-MB-231细胞与ZR-75-1细胞生长的作用,使用细胞集落形成实验研究其在低氧环境下对无叶酸培养基中MDA-MB-231细胞、有叶酸培养基中MDA-MB-231细胞及ZR-75-1细胞放疗敏感性的影响。利用流式细胞术研究叶酸修饰稀土改性载氧碳纳米管联合放疗干预MDA-MB-231乳腺癌细胞株的凋亡率的改变。利用Western Blot实验观察Bcl-2、survivin、Hif-1α、Rad51及Ku80表达水平的改变。结果:在常氧及低氧环境下,叶酸修饰稀土改性载氧碳纳米管在低于100μg/ml的浓度时对乳腺癌细胞株生长无明显影响。在低氧环境下,放疗联合叶酸修饰稀土改性载氧碳纳米管组相比于单纯放疗组细胞克隆形成率有不同程度的降低,以无叶酸培养基中MDA-MB-231细胞组降低最为明显,照射剂量在2、4、6、8Gy时其细胞克隆形成率均显著降低(P<0.05)。流式细胞术显示叶酸修饰稀土改性载氧碳纳米管联合放疗后可使MDA-MB-231乳腺癌细胞株的凋亡率增加。Western Blot实验显示Bcl-2、Survivin、Hif-1α、Rad51及Ku80表达水平均降低。结论:叶酸修饰稀土改性载氧碳纳米管可在体外低氧环境下增强乳腺癌细胞株对放疗的敏感性。
Objective: To study the effect of folate-modified rare earth-modified carbon nanotubes on the radiosensitivity of breast cancer cell lines in hypoxia. Methods: The effect of folic acid-modified rare earth-modified carbon nanotubes on the growth of MDA-MB-231 cells and ZR-75-1 cells was studied by water-soluble tetrazolium salt method (WST- On the radiosensitivity of MDA-MB-231 cells in folic acid-free medium, MDA-MB-231 cells in folic acid medium and ZR-75-1 cells in hypoxia environment. Flow cytometry was used to study the changes of apoptosis induced by folate-modified rare earth-modified carbon nanotubes combined with radiotherapy in MDA-MB-231 breast cancer cell line. The expression of Bcl-2, survivin, Hif-1α, Rad51 and Ku80 was detected by Western Blot. RESULTS: Under normoxia and hypoxia conditions, folinic acid modified rare earth-modified carbon nanotubes had no significant effect on the growth of breast cancer cell lines when the concentration was lower than 100μg / ml. In hypoxic environment, the rate of cell colony formation in radiotherapy combined with folate-modified rare earth-modified carbon nanotubes group decreased to some extent compared with that in radiotherapy alone group, and decreased in MDA-MB-231 cells group Obviously, the cell colony formation rate was significantly decreased at 2, 4, 6, 8 Gy (P <0.05). Flow cytometry showed that folic acid modified rare earth modified carbon nanotubes combined with radiotherapy could increase the apoptosis rate of MDA-MB-231 breast cancer cell lines. Western Blot experiments showed that the expression of Bcl-2, Survivin, Hif-1α, Rad51 and Ku80 decreased. CONCLUSION: Folic acid modified rare earth modified carbon nanotubes can enhance the sensitivity of breast cancer cell lines to radiotherapy in vitro under hypoxia.