Li Xinyue,Yin Jun,Zhang Xuxia,et al.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 NameAffiliationE-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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