Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1.
Low dose of kaempferol suppresses the migration and invasion of triple-negative breast cancer cells by downregulating the activities of RhoA and Rac1.
复制标题
低剂量山奈酚通过下调RhoA和Rac1活性抑制三阴性乳腺癌细胞的迁移和侵袭
DOI：
10.2147/ott.s140886
复制
发表时间：
2017
影响因子：
4
通讯作者：
Zhu Y
中科院分区：
文献类型：
--
作者：
Li S;Yan T;Deng R;Jiang X;Xiong H;Wang Y;Yu Q;Wang X;Chen C;Zhu Y
目的三阴性乳腺癌（TNBC）是一种侵袭性强、治疗困难的疾病。虽然已经报道了山奈酚在乳腺癌中的抗癌作用，但山奈酚对TNBC的影响仍不清楚。材料和方法本实验研究了低剂量山奈酚在TNBC细胞中的迁移抑制作用。使用伤口愈合测定和细胞侵袭测定来确认用山奈酚或转染的指定构建体处理的细胞的迁移和侵袭。我们用Rho活化测定法评估了TNBC细胞中RhoA、Rac 1和Cdc 42的活化。一组雌激素受体/孕酮受体/人表皮生长因子受体2（ER/PR/HER 2）抑制剂处理非TNBC（SK-BR-3和MCF-7）细胞并阻断ER/PR/HER 2活性。采用伤口愈合测定和Rho活化测定来测量山奈酚和ER/PR/HER 2抑制剂对Rho活化和细胞迁移速率的影响。结果低浓度山奈酚（20 μmol/L）对TNBC细胞的迁移和侵袭能力有明显的抑制作用，但对非TNBC细胞（SK-BR-3和MCF-7）的迁移能力无明显影响。低剂量山奈酚下调TNBC细胞RhoA和Rac 1的激活。此外，低剂量山奈酚还能抑制HER 2沉默的SK-BR-3和ER/PR沉默的MCF-7细胞的迁移和RhoA激活。过表达的HER 2挽救了经山奈酚处理的MDA-MB-231细胞的细胞迁移和RhoA和Rac 1激活。结论低剂量山奈酚通过阻断RhoA和Rac 1信号通路抑制TNBC细胞的迁移和侵袭。
Purpose Triple-negative breast cancer (TNBC) is an especially aggressive and hard-to-treat disease. Although the anticancer role of kaempferol has been reported in breast cancer, the effect of kaempferol on TNBC remains unclear. Materials and methods This experiment investigated the migration-suppressive role of a low dose of kaempferol in TNBC cells. Wound-healing assays and cell invasion assays were used to confirm the migration and invasion of cells treated with kaempferol or transfected indicated constructs. We evaluated the activations of RhoA, Rac1 and Cdc42 in TNBC cells with a Rho activation assay. A panel of inhibitors of estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 (ER/PR/HER2) treated non-TNBC (SK-BR-3 and MCF-7) cells and blocked the ER/PR/HER2 activity. Wound-healing assays and Rho activation assays were employed to measure the effect of kaempferol and ER/PR/HER2 inhibitors on Rho activation and cell migration rates. Results A low dose of kaempferol (20 μmol/L) had a potent inhibitory effect on the migration and invasion of TNBC cells, but not on the migration of non-TNBC (SK-BR-3 and MCF-7) cells. The low dose of kaempferol downregulated the activations of RhoA and Rac1 in TNBC cells. Moreover, the low dose of kaempferol also inhibited the migration and RhoA activations of HER2-silence SK-BR-3 and ER/PR-silence MCF-7 cells. Overexpressed HER2 rescued the cell migration and RhoA and Rac1 activations of kaempferol-treated MDA-MB-231 cells. Conclusion The low dose of kaempferol inhibits the migration and invasion of TNBC cells via blocking RhoA and Rac1 signaling pathway.