Hinokiflavone is a natural product, isolated from Selaginella P. Beauv, Juniperus phoenicea and Rhus succedanea. Even though hinokiflavone was reported to possess cytotoxicity to many cancer cells, and has potential in cancer treatment, the anti-proliferation and anti-metastasis efficacy of hinokiflavone on human breast cancer cells has not a further research. In this study, we investigated the anti-cancer activity of hinokiflavone in human breast cancer cells in vitro and in vivo. Hinokiflavone exhibited a time- and dose-dependent manner apoptosis induction by upregulating expression of Bax and downregulating Bcl-2 in breast cancer cells. Furthermore, hinokiflavone significantly inhibited the migration and invasion of breast cancer cells by impairing the process of epithelial-to-mesenchymal transition. In addition, the tumour growth was distinctly inhibited by treatment of hinokiflavone in a xenograft tumour mouse model of MDA-MB-231 cells. Immunohistochemical analysis of tumour sections showed that MMP-2+ cells and Ki-67+ cells were remarkably decreased in tumour tissues of mice after treatment of hinokiflavone, indicating that hinokiflavone inhibits not only proliferation but also metastasis of breast cancer cells. Our study suggested that hinokiflavone can be a potential drug to breast cancer. SIGNIFICANCE OF THE STUDY: Hinokiflavone significantly inhibited proliferation and induced apoptosis in breast cancer cells. In addition, hinokiflavone remarkably inhibited migration and invasion of breast cancer cells via EMT signalling pathway. It is worth noting that hinokiflavone possesses anti-tumour effect in tumour mouse xenograft model of breast cancer. Overall, our results indicated that hinokiflavone may be a potential anticancer drug for breast cancer treatment.

中文翻译：

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Hinokiflavone通过EMT信号传导途径诱导凋亡并抑制乳腺癌细胞的迁移。

Hinokiflavone是天然产物，从卷柏（Selaginella P. Beauv），杜松（Juniperus phoenicea）和大戟（Rus succedanea）中分离。尽管已经报道了hinokiflavone对许多癌细胞具有细胞毒性，并且在癌症治疗方面具有潜力，但是hinokiflavone对人乳腺癌细胞的抗增殖和抗转移功效尚无进一步研究。在这项研究中，我们研究了人肝癌细胞中人诺基黄酮的体外和体内抗癌活性。Hinokiflavone通过上调乳腺癌细胞中Bax的表达和下调Bcl-2来表现出时间依赖性和剂量依赖性。此外，hinokiflavone通过损害上皮到间充质的转化过程，显着抑制乳腺癌细胞的迁移和侵袭。此外，在MDA-MB-231细胞异种移植肿瘤小鼠模型中，hinokiflavone处理可明显抑制肿瘤的生长。肿瘤切片的免疫组织化学分析显示，在接受hinokiflavone治疗后，小鼠肿瘤组织中MMP-2 +细胞和Ki-67 +细胞显着减少，表明hinokiflavone不仅抑制乳腺癌细胞的增殖，而且抑制其转移。我们的研究表明，hinokiflavone可能是乳腺癌的潜在药物。该研究的意义：Hinokiflavone显着抑制乳腺癌细胞的增殖并诱导其凋亡。此外，hinokiflavone通过EMT信号通路显着抑制乳腺癌细胞的迁移和侵袭。值得注意的是，hinokiflavone在乳腺癌的肿瘤小鼠异种移植模型中具有抗肿瘤作用。