目的：探讨人乳腺癌易感基因1（breast cancer susceptibility gene 1, BRCA1）通过Wnt/β-catenin通路对非小细胞肺癌（non-small cell lung cancer，NSCLC）H1650 细胞增殖、迁移和侵袭的影响。方法：采用 WB 法和 qPCR 法检测 NSCLC 细胞系A549、H1299、H1650和正常肺上皮细胞 BEAS-2B中BRCA1 mRNA和蛋白的表达水平。在H1650细胞中构建稳定BRCA1过表达细胞株（LV-BRCA1），实验分为空白对照组（NC）、阴性对照组（LV-BRCA1-NC）、实验组（LV-BRCA1）和抑制剂组（LV-BRCA1+XAV-939）。用MTT法、划痕愈合实验和Transwell小室法分别检测各组细胞的增殖、迁移和侵袭能力，WB法检测细胞中BRCA1、cyclin D1、β-catenin、c-Myc和Cox2蛋白的表达水平。结果：NSCLC细胞中BRCA1 mRNA和蛋白的表达水平均显著高于BEAS-2B细胞（均P<0.01）。上调BRCA1可显著提高H1650细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01），上调细胞中cyclin D1、β-catenin、c-Myc、Cox2和c-Jun蛋白的表达（P<0.05或P<0.01）；XAV-939可显著下调过表达BRCA1细胞的增殖、迁移和侵袭能力（P<0.05或P<0.01），并降低细胞中cyclin D1、β-catenin、c-Myc、Cox2和c-Jun蛋白的表达（P<0.05或P<0.01）。结论：BRCA1通过激活Wnt/β-catenin通路促进NSCLC H1650细胞的增殖、迁移与侵袭，其有望成为NSCLC诊断标志物和治疗靶标。

Objective: To investigate the effect of breast cancer susceptibility gene 1 (BRCA1) on the proliferation, migration and invasion of non-small cell lung cancer (NSCLC) H1650 cells through Wnt/β-catenin pathway. Methods: WB and qPCR were used to detect the mRNA and protein expressions of BRCA1 in NSCLC A549, H1299, H1650 cells and normal lung epithelial BEAS-2B cell. A stable BRCA1 over-expression cell line (LV-BRCA1) was constructed in H1650 cells, and blank control group (NC), negative control group (LV-BRCA1-NC), experimental group (LV-BRCA1) and inhibitor group (LV-BRCA1+XAV-939) were set up. The proliferative activity of cells in each group was detected by MTT assay, the migration ability of cells was detected by scratch test, the invasive ability of cells was detected by Transwell method, and the protein expression levels of BRCA1, cyclin D1, β-catenin, c-Myc and Cox2 were detected by WB. Results: The mRNA and protein expression levels of BRCA1 in NSCLC cells were significantly higher than those in BEAS-2B cells (all P<0.01). Up-regulation of BRCA1 expression in H1650 cells could significantly enhance cell proliferation, migration and invasion (P<0.05 or P<0.01), and increase the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01). β-catenin inhibitor XAV-939 significantly down-regulated the proliferation, migration and invasion ability of H1650 cells overexpressing BRCA1, and decreased the protein expressions of cyclin D1, β -catenin, c-Myc, Cox2 and c-Jun (P<0.05 or P<0.01).Conclusion: BRCA1 can promote the proliferation, migration and invasion of NSCLC H1650 cells by activating Wnt/β-catenin pathway,and it is expected to be a potential diagnostic biomarker and treatment target for NSCLC.

北京市卫生科技发展专项基金资助项目（No.2017-1-237）