Li Xinyue,Yin Jun,Zhang Xuxia,Zhong Dengqin,Chen Yu,Chen Honghong.Radiosensitization effect of Ta4C3-PVP nanosheets on xenograft tumor in mice bearing 4T1 murine triple-negative breast cancer[J].Chinese Journal of Radiological Medicine and Protection,2021,41(4):241-246 |
Radiosensitization effect of Ta4C3-PVP nanosheets on xenograft tumor in mice bearing 4T1 murine triple-negative breast cancer |
Received:November 03, 2020 |
DOI:10.3760/cma.j.issn.0254-5098.2021.04.001 |
KeyWords:Ta4C3-PVP nanosheets Radiosensitization Triple-negative breast cancer |
FundProject:国家自然科学基金(31370839) |
Author Name | Affiliation | E-mail | Li Xinyue | Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China | | Yin Jun | Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China | | Zhang Xuxia | Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China | | Zhong Dengqin | Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China | | Chen Yu | College of Life Science, Shanghai University, Shanghai 200444, China | | Chen Honghong | Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China | hhchen@shmu.edu.cn |
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Abstract:: |
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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