| 李欣悦,尹俊,张旭霞,钟登琴,陈雨,陈红红.Ta4C3-PVP纳米片对4T1三阴性乳腺癌小鼠移植瘤的放射增敏作用[J].中华放射医学与防护杂志,2021,41(4):241-246 |
| Ta4C3-PVP纳米片对4T1三阴性乳腺癌小鼠移植瘤的放射增敏作用 |
| Radiosensitization effect of Ta4C3-PVP nanosheets on xenograft tumor in mice bearing 4T1 murine triple-negative breast cancer |
| 投稿时间：2020-11-03 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.04.001 |
| 中文关键词: Ta4C3-PVP纳米片 放射敏感性 三阴性乳腺癌 |
| 英文关键词:Ta4C3-PVP nanosheets Radiosensitization Triple-negative breast cancer |
| 基金项目:国家自然科学基金（31370839） |
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| 摘要点击次数: 2062 |
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| 中文摘要: |
| 目的 研究Ta4C3-PVP纳米片对三阴性乳腺癌4T1细胞小鼠移植瘤的放射增敏作用。方法 于雌性BALB/c小鼠右侧腹皮下注射4T1细胞建立4T1荷瘤小鼠模型，按肿瘤体积大小均匀分为空白对照组、单纯Ta4C3-PVP组、单纯照射组、Ta4C3-PVP联合照射组。尾静脉注射20 mg/kg Ta4C3-PVP预处理24 h后给予8 Gy单次肿瘤局部X射线照射，测量移植瘤体积、瘤重，检测肿瘤细胞增殖标志物Ki-67蛋白表达、DNA双链断裂（DSBs）分子标志物γ-H2AX焦点形成，绘制肿瘤生长曲线并计算放射增敏系数（EF）及抑瘤率。结果 与空白对照组相比，单纯照射组、Ta4C3-PVP联合照射组于照射后16 d均能明显抑制肿瘤生长（t=5.41、9.59，P<0.05）、降低瘤重（t=2.67、4.40，P<0.05），其中Ta4C3-PVP联合照射组的EF达1.57，抑瘤率约为64%，明显优于单纯照射组（42%）。免疫组织化学结果显示，与空白对照组相比，单纯照射组和Ta4C3-PVP联合照射组肿瘤细胞Ki-67蛋白表达受到明显抑制（t=5.73、8.02，P<0.05）、γ-H2AX焦点产额明显增加（t=2.97、9.86，P<0.05），且Ta4C3-PVP联合照射组较单纯照射组Ki-67表达抑制更显著（t=4.75，P<0.05）、γ-H2AX焦点产额更多（t=4.42，P<0.05）。结论 Ta4C3-PVP纳米片可通过增加射线诱导的DNA DSBs，增强4T1荷瘤小鼠移植瘤的放射敏感性。 |
| 英文摘要: |
| Objective To investigate the radiosensitizing effect of Ta4C3-PVP nanosheets on the tumor of 4T1 murine triple-negative breast cancer cells planted in mice. Methods 4T1 tumor-bearing mice model was established by subcutaneous injection of 4T1 cells into the right flank of the female BALB/c mice. The mice were divided into four groups uniformly according to their tumor size:blank control group, Ta4C3-PVP group, ionizing radiation (IR) group and Ta4C3-PVP plus IR group. A single dose of 8 Gy X-ray local irradiation was given to xenograft tumor at 24 h after tail intravenous injection of Ta4C3-PVP (20 mg/kg). The xenograft tumor volume and weight, the pathological changes of tumor tissue, the expression of tumor proliferative marker Ki-67 protein, and the formation of γ-H2AX foci[a DNA double-strand breaks (DSBs) molecular marker] were detected. Tumor growth curve was established, and enhancement factor (EF) and tumor inhibition rate were calculated. Results Compared with the blank control group, tumor growth was significantly inhibited (t=5.41, 9.59, P<0.05) and tumor weight was markedly decreased (t=2.67, 4.40, P<0.05) in both IR group and Ta4C3-PVP plus IR group at day 16 after IR. The EF in Ta4C3-PVP plus IR group was 1.57, and tumor inhibition rate in Ta4C3-PVP plus IR group were about 64%, which was much higher than that of IR group alone(42%). Immunohistochemistry and immunofluorescence histochemistry assays showed that the expression of Ki-67 protein was obviously decreased and the amount of γ-H2AX foci was significantly increased in both IR group and Ta4C3-PVP plus IR group in comparison with the blank control group (t=5.73, 8.02, 2.97, 9.86, P<0.05). Moreover, the inhibition of Ki-67 protein expression and the increase of γ-H2AX foci were much higher in Ta4C3-PVP plus IR group than that in IR group (t=4.75, 4.42, P<0.05). Conclusions Ta4C3-PVP nanosheets could enhance radiosensitivity of xenograft tumor in 4T1 tumor-bearing mice through increasing the IR-induced DNA DSBs. |
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