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巴马汀可减弱三阴性乳腺癌细胞的肺转移定植。

Palmatine Attenuates Metastatic Lung Colonization of Triple Negative Breast Cancer Cells.

作者信息

Ativui Selase, Danquah Cynthia A, Ossei Paul Poku Sampene, Ofori Michael

机构信息

Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

Department of Pathology, School of Medical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.

出版信息

Front Pharmacol. 2022 Apr 13;13:853230. doi: 10.3389/fphar.2022.853230. eCollection 2022.

Abstract

Metastatic breast cancer to the lungs is a serious, life-threatening complication that is difficult to cure. Circulating tumor cells play a key role in the metastatic spread of breast cancer to the lungs the lymphatic or circulatory system. Palmatine is a protoberberine alkaloid, identified as an active component of traditional African herbal preparations. Palmatine has antimetastatic and antiproliferative effects. The inhibitory activity of palmatine on the metastatic colonization of triple negative breast cancer cells in the lungs was investigated in this study. 4T1 triple breast cancer cells were transplanted synergically to the thoracic duct of the female balb/c mice the lymphatic system. Palmatine 1, 5 and 10 mg/kg were administered for 28 days. The lungs were analyzed for levels of arterial blood gas, histological damage, immunohistochemical expression of the metastasis-associated protein 1 (MTA1) and tumor suppressor p53 (p53). Administering palmatine 1-10 mg/kg dose dependently improved hypoxemia, ameliorated metastasis associated lung injury; histology score of 3.33 ± 0.33, 1.67 ± 0.33, 1.33 ± 0.33, decreased lung MTA1 (2.19 ± 0.12, 1.83 ± 0.04, 1.84 ± 0.05) and increased p53 expression (1.99 ± 0.06, 2.27 ± 0.12, 2.34 ± 0.12) respectively. Palmatine preserved lung morphology and demonstrated therapeutic potential in aiding the treatment of lung metastasis.

摘要

转移性乳腺癌至肺部是一种严重的、危及生命的并发症,难以治愈。循环肿瘤细胞在乳腺癌向肺部的转移扩散(通过淋巴或循环系统)中起关键作用。巴马汀是一种原小檗碱生物碱,被确定为传统非洲草药制剂的活性成分。巴马汀具有抗转移和抗增殖作用。本研究调查了巴马汀对三阴性乳腺癌细胞在肺部转移定植的抑制活性。将4T1三阴性乳腺癌细胞协同移植到雌性balb/c小鼠的胸导管(通过淋巴系统)。给予巴马汀1、5和10mg/kg,持续28天。分析肺部的动脉血气水平、组织学损伤、转移相关蛋白1(MTA1)和肿瘤抑制因子p53(p53)的免疫组化表达。给予1 - 10mg/kg剂量的巴马汀可剂量依赖性地改善低氧血症,减轻与转移相关的肺损伤;组织学评分分别为3.33±0.33、1.67±0.33、1.33±0.33,肺MTA1降低(2.19±0.12、1.83±0.04、1.84±0.05),p53表达增加(1.99±0.06、2.27±0.12、2.34±0.12)。巴马汀保持了肺形态,并显示出在辅助治疗肺转移方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a9a3/9043321/ee48352ae40c/fphar-13-853230-g001.jpg

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