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防己黄芪汤抑制 MDA-MB-231 细胞体外侵袭,并降低三阴性乳腺癌异种移植肿瘤斑马鱼模型中的肿瘤生长和转移。

Fangjihuangqi Decoction inhibits MDA-MB-231 cell invasion in vitro and decreases tumor growth and metastasis in triple-negative breast cancer xenografts tumor zebrafish model.

机构信息

Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China.

Beijing University of Chinese Medicine Fangshan Traditional Medical Hospital, Beijing University of Chinese Medicine, Beijing, China.

出版信息

Cancer Med. 2020 Apr;9(7):2564-2578. doi: 10.1002/cam4.2894. Epub 2020 Feb 9.

Abstract

Triple-negative breast cancer (TNBC) is a basal-like cancer which is considered to be more intrusive, have a poorer prognosis and chemoresistance. TNBC is characterized by the presence of epithelial to mesenchymal transition (EMT) that plays a major role in the progression of the cancer. In the present study, we first use a classic prescription of Chinese medicine Fangjihuangqi Decoction to treat TGFβ1-induced MDA-MB-231 cells in vitro. Our data showed that TGFβ1-induced MDA-MB-231 cell morphology change, promoted MDA-MB 231 invasion, increased Vimentin expression, and decreased E-cadherin expression. Further, Fangjihuangqi Decoction-medicated serum (FHS) treated both MDA-MB 231 cells and TGFβ1-induced MDA-MB-231 cells. Results showed that Fangjihuangqi Decoction could inhibit cell proliferation, reduce cell invasion, increase E-cadherin expression, and decrease EMT markers. Secondly, we established a xenograft tumor zebrafish model to assess Fangjihuangqi Decoction inhibition of cancer cell proliferation and invasion. Our results indicated that Fangjihuangqi Decoction could inhibit tumor growth, restrain the sprouts number of tumor neovascularization, and reduce the length of tumor neoplastic lymphatics by increasing E-cadherin expression and decreasing EMT markers in TNBC xenograft tumor zebrafish model. Overall, our studies provide evidences that Fangjihuangqi Decoction could inhibit TNBC, reverse EMT, and contribute to antimetastasis by increasing E-cadherin expression and decreasing EMT markers, which provide an experimental basis for clinical application of Fangjihuangqi Decoction on TNBC treatment.

摘要

三阴性乳腺癌(TNBC)是一种基底样癌症,被认为更具侵袭性,预后更差,且对化疗有耐药性。TNBC 的特征是存在上皮间质转化(EMT),这在癌症的进展中起着主要作用。在本研究中,我们首先使用中药方剂复方黄芪汤治疗 TGFβ1 诱导的 MDA-MB-231 细胞体外。我们的数据表明,TGFβ1 诱导的 MDA-MB-231 细胞形态发生变化,促进 MDA-MB 231 侵袭,增加波形蛋白表达,降低 E-钙黏蛋白表达。此外,复方黄芪汤给药血清(FHS)处理 MDA-MB 231 细胞和 TGFβ1 诱导的 MDA-MB-231 细胞。结果表明,复方黄芪汤可抑制细胞增殖,减少细胞侵袭,增加 E-钙黏蛋白表达,降低 EMT 标志物。其次,我们建立了一个异种移植肿瘤斑马鱼模型来评估复方黄芪汤对癌细胞增殖和侵袭的抑制作用。我们的结果表明,复方黄芪汤可以抑制肿瘤生长,抑制肿瘤新生血管的芽生,减少肿瘤新生淋巴管的长度,通过增加 E-钙黏蛋白表达和降低 EMT 标志物在 TNBC 异种移植肿瘤斑马鱼模型中。总的来说,我们的研究提供了证据表明,复方黄芪汤可以抑制 TNBC,逆转 EMT,并通过增加 E-钙黏蛋白表达和降低 EMT 标志物来抑制转移,为复方黄芪汤在 TNBC 治疗中的临床应用提供了实验依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b6/7131862/2813ffb1a48f/CAM4-9-2564-g001.jpg

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