| 尹俊,李欣悦,张旭霞,王梦梦,陈雨,陈红红.Ta4C3-PVP纳米片对三阴性乳腺癌MDA-MB-231细胞的放射增敏作用[J].中华放射医学与防护杂志,2020,40(7):493-499 |
| Ta4C3-PVP纳米片对三阴性乳腺癌MDA-MB-231细胞的放射增敏作用 |
| Radiosensitzation effect of Ta4C3-PVP nanosheets in human triple-negative breast cancer MDA-MB-231 cells |
| 投稿时间：2020-01-16 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.07.001 |
| 中文关键词: 碳化钽 纳米片 放射增敏 三阴性乳腺癌 |
| 英文关键词:Tantalum carbide Nanosheets Radiosensitization Triple-negative breast cancer |
| 基金项目:国家自然科学基金（31300694，81673091） |
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| 摘要点击次数: 1961 |
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| 中文摘要: |
| 目的 研究聚乙烯吡咯烷酮（PVP）修饰的碳化钽（Ta4C3）纳米片对人三阴性乳腺癌MDA-MB-231细胞放射敏感性的影响。方法 合成并表征Ta4C3-PVP纳米片。利用荧光显微镜观察MDA-MB-231细胞对异硫氰酸荧光素（FITC）标记Ta4C3-PVP纳米片的摄取情况。CCK-8法检测不同浓度的Ta4C3-PVP纳米片对MDA-MB-231细胞的毒性。将MDA-MB-231细胞分为空白对照组、Ta4C3-PVP组、单纯照射组和Ta4C3-PVP+照射组，克隆形成试验检测细胞放射敏感性的改变，酶标仪检测细胞内活性氧（ROS）水平和脂质氧化产物丙二醛（MDA）含量，免疫荧光法检测DNA双链断裂（DSBs）分子标志物γH2AX焦点形成及有丝分裂灾难形成。结果 成功合成Ta4C3-PVP纳米片，呈薄片形貌，水动力直径和厚度分别约为143.93和1.35 nm。FITC标记的Ta4C3-PVP被MDA-MB-231细胞摄取后主要分布于细胞质中。Ta4C3-PVP纳米片在浓度高达400 μg/ml时，对MDA-MB-231细胞无明显毒性。克隆形成试验结果显示，50和100 μg/ml Ta4C3-PVP预处理使受照MDA-MB-231细胞的存活曲线分别较单纯照射组下移，且呈浓度依赖性，低、高浓度Ta4C3-PVP预处理的放射增敏比（SERD0）分别为1.21和1.45。Ta4C3-PVP+照射组于照射后2和12 h细胞内ROS水平均明显高于单纯照射组（q=20.01、7.193，P< 0.05），于照射后1、4和8 h Ta4C3-PVP+照射组含≥ 5个γH2AX焦点的阳性细胞率均明显高于单纯照射组（q=36.78、14.87、8.217，P< 0.05），Ta4C3-PVP+照射组于照射后24和48 h的MDA含量均明显高于单纯照射组（q=14.02、7.015，P< 0.05），Ta4C3-PVP+照射组于照射后72 h的有丝分裂灾难比例明显高于单纯照射组（q=16.33，P< 0.05）。结论 Ta4C3-PVP纳米片通过提高辐射诱导的ROS水平增强人三阴性乳腺癌MDA-MB-231细胞的放射敏感性。 |
| 英文摘要: |
| Objective To assess the radiosensitivity of polyvinylpyrrolidone (PVP) modified tantalum carbide (Ta4C3) nanosheets in human triple-negative breast cancer MDA-MB-231 cells in vitro. Methods PVP-modified Ta4C3 nanosheets were synthesized and characterized. The uptake of fluoresceine isothiocyanate(FITC) labeled Ta4C3-PVP nanosheets in MDA-MB-231 cells was examined by fluorescent microscope. The toxicity of Ta4C3-PVP in the cells was measured by CCK-8 assay.These cells were divided into 4 groups:control group, Ta4C3-PVP group, irradiation group alone and Ta4C3-PVP plus irradiation group. The colony formation assay was used to evaluate the radiosensitivity. The levels of intracellular reactive oxygen species (ROS) and lipid oxidation production, malondialdehyde (MDA), were detected with an automatic microplate reader.γH2AX foci and mitotic catastrophe were observed by immunofluorescence staining. Results Ta4C3-PVP nanosheets with a single-layer flaky shape were successfully synthesized. The hydrodynamic diameter and thick of Ta4C3-PVP nanosheets were about 143.93 nm and 1.35 nm, respectively. The FITC labeled Ta4C3-PVP nanosheets were uptaken by MDA-MB-231 cells, which was mainly distributed in the cytoplasm.Treatment of Ta4C3-PVP nanosheets at concentrations up to 400 μg/ml was noncytotoxic to MDA-MB-231 cells. The colony formation assay showed that pretreatment with Ta4C3-PVP at 50 and 100 μg/ml moved the survival curve of the irradiated cells downward in a concentration-dependent manner, compared to irradiation group alone. The sensitization enhancement ratio (SERD0) of Ta4C3-PVP at 50 and 100 μg/ml were 1.21 and 1.45, respectively.The intracellular ROS level in Ta4C3-PVP plus irradiation group was significantly higher than that in irradiation group alone at 2 and 12 h after irradiation (q=20.01, 7.193, P<0.05). The percentage of positive cells with more than five γH2AX foci in Ta4C3-PVP plus irradiation group was higher than that of irradiation group alone at 1, 4 and 8 h after irradiation (q=36.78, 14.87, 8.217, P<0.05). The content of MDA in Ta4C3-PVP plus irradiation group was significantly higher than that of irradiation group alone at 24 and 48 h after irradiation (q=14.02, 7.015, P<0.05). The percentage of cells that succumbed to mitotic catastrophe in Ta4C3-PVP plus irradiation group was significantly higher than that in irradiation group alone at 72 h after irradiation (q=16.33, P<0.05). Conclusions Ta4C3-PVP nanosheets could enhance the radiosensitivity of human triple-negative breast cancer MDA-MB-231 cells through an increase of the intracellular ROS induced by irradiation. |
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