Radiosensitization effect of Ta 4C 3-PVP nanosheets on xenograft tumor in mice bearing 4T1 murine triple-negative breast cancer / 中华放射医学与防护杂志

ABSTRACT

Objective:To investigate the radiosensitizing effect of Ta 4C 3-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, Ta 4C 3-PVP group, ionizing radiation (IR) group and Ta 4C 3-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 Ta 4C 3-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 Ta 4C 3-PVP plus IR group at day 16 after IR. The EF in Ta 4C 3-PVP plus IR group was 1.57, and tumor inhibition rate in Ta 4C 3-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 Ta 4C 3-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 Ta 4C 3-PVP plus IR group than that in IR group ( t=4.75, 4.42, P < 0.05). Conclusions:Ta 4C 3-PVP nanosheets could enhance radiosensitivity of xenograft tumor in 4T1 tumor-bearing mice through increasing the IR-induced DNA DSBs.