关键词: 乳腺癌, ATR 抑制剂, Brahma 相关基因 1, 重组酶 51, 乳腺癌易感基因 2 定位协作蛋白

Abstract: Objective To explore the effect of ATR inhibitor combined with carboplatin treatment on the growth of breast cancer xenografts in nude mice and its influences on Brahma related gene 1 (BRG1), recombinase 51 (RAD51) and breast cancer susceptibility gene 2 localization collaboration protein ( PALB2) expression in tumor tissues. Methods A total of 40 nude mice bearing breast cancer xenografts were randomly divided into control group, carboplatin group, ATR inhibitor M6620 group and carboplatin + M6620 group (n = 10). The volume and mass of the tumors were measured, the mRNA and protein expression levels of Ki67, MMP2, N-cadherin and E-cadherin were detected by RT-qPCR and Western blotting. The expression levels of BRG1, RAD51, PALB2 proteins were determined by immunohistochemistry. Results The mass and volume of the tumors, the expression levels of Ki67, MMP2, N-cadherin, and the expression levels of BRG1, RAD51, PALB2 proteins in the carboplatin group and the M6620 group were significantly lower than those in the control group, while the expression level of E-cadherin was significantly higher than that in control group (P< 0. 05). The mass and volume of the tumors, the expression levels of Ki67, MMP2, N-cadherin, and expression levels of BRG1, RAD51, PALB2 proteins in the carboplatin + M6620 group were significantly lower than those in the carboplatin group and those in the M6620 group, while the expression level of E-cadherin was significantly higher than that in the carboplatin group and that in the M6620 group (P< 0. 05). Conclusion The treatment of ATR inhibitor combined with carboplatin could significantly inhibit the growth of breast cancer xenografts inude mice, and inhibit the expression of BRG1, RAD51 and PALB2 in tumor tissues.

Key words: breast cancer, ATR inhibitor, Brahma related gene 1, recombinase 51, breast cancer susceptibility gene 2 localization collaboration protein