阿帕替尼通过调节胞外信号调节激酶1/2途径对乳腺癌小鼠模型抑瘤率及肿瘤细胞凋亡的影响.

OBJECTIVE: To probe into the effects of apatinib on tumor inhibition rate and tumor cell apoptosis in breast cancer mouse model by regulating extracellular regulated kinase ( ERK) 1 / 2 pathway. METHODS: Human breast cancer cell line MCF-7 cells were inoculated in the right chest wall of nude mice, which were randomly divided into control group, low-dose group[10 mg / (kg·d) of Apatinib] and high-dose group[30 mg / ( kg·d) of Apatinib] after successful modeling, with 12 mice in each group. After intragastric administration once a day for 21 days, the tumor growth curves of three groups were plotted and the tumor inhibition rates were compared. After the last administration, the mice were executed and the tumor tissues were collected, the expression of ERK1 / 2 pathwayrelated proteins [ERK1 / 2, phosphorylated ERK1 / 2(p-ERK1 / 2)] in the tumor tissues was detected by Western blot. The effects of apatinib on MCF-7 cell cycle distribution and cell apoptosis were detected by flow cytometry. RESULTS: After processing with different concentrations of apatinib, the differences in apoptosis rate and the proportion of MCF-7 cells distributed in G0 -G1 phase were statistically significant ( P < 0. 05), among which the apoptosis rate and the proportion of MCF-7 cells distributed in G0 -G1 phase were significantly higher in the group given 20 μmol / L of apatinib than in the other low concentration groups, with statistically significant differences (P<0. 05). The tumor volumes of mice in the high-dose and low-dose groups were significantly lower than that of the control group at the 6th to 21st day of administration, with statistically significant differences (P<0. 05), of which the tumor volumes of mice in the highdose group were the smallest. The mean tumor weights of the high-dose group and low-dose group on the 22nd day were respectively (0. 343±0. 089) g and (0. 658±0. 145) g, which were significantly lower than that of the control group[(1. 163±0. 231) g], with statistically significant differences(P<0. 05). The tumor inhibition rates of the highdose group and low-dose group were respectively 64. 46% and 34. 07%, and there was a dose dependence. The expression levels of ERK1 / 2 and p-ERK1 / 2 in mice in the high-dose group and low-dose group were significantly lower than those in the control group, with statistically significant difference (P<0. 05), of which the expression levels of ERK1 / 2 and p-ERK1 / 2 in mice in the high-dose group were the lowest. CONCLUSIONS: Apatinib can effectively inhibit the ERK1 / 2 signaling pathway in breast cancer cell, induce apoptosis and proliferation of tumor cells, and thus inhibit the growth of tumors in breast cancer mice. [ABSTRACT FROM AUTHOR]