College of Food Science and Technology, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.
College of Bioscience and Biotechnology, Shenyang Agricultural University, Shenyang, Liaoning 110866, China.
Food Funct. 2020 Sep 23;11(9):7481-7494. doi: 10.1039/d0fo01531h.
Pilose antler (PA) is a traditional Chinese functional food that has been reported to inhibit breast cancer; however, the specific substances that exert this effect and the underlying mechanisms remain unknown. This study aims to identify the specific proteins in PA water-soluble polypeptides (PAWPs) that are involved in cancer inhibition and determine the effects of PAWPs on triple-negative breast cancer in mice. In this study, peptidomic analysis of 105 varieties of polypeptides from PAWPs was carried out using LC-MS, 22 of which had functions that could potentially suppress tumors, including endopeptidase inhibitors, metal ion-binding proteins, angiogenesis inhibitors, intercellular adhesion proteins, and extracellular matrix repair proteins. Furthermore, we showed that intragastric administration of PAWPs into mice inhibited the growth and metastasis of triple-negative 4T1 breast tumors. PAWPs activated the expression of cleaved-caspase3 and increased tumor apoptosis, resulting in the reduction of platelet-endothelial cell adhesion molecule (PECAM-1/CD31) expression and the number of blood vessels, as well as the inhibition of matrix metalloproteinase (MMP) 2 and 9, increasing the ratio of Cadherin-1 (CDH1)/Cadherin-2 (CDH2) and inhibiting epithelial-mesenchymal transition (EMT) in these tumors. Therefore, PAWPs inhibit the progression and metastasis of triple-negative 4T1 breast cancer at multiple key sites in mice and contain various tumor suppressor proteins that are potentially involved in these processes.
鹿茸（PA）是一种传统的中药，据报道其具有抑制乳腺癌的作用；然而，发挥这种作用的具体物质及其潜在机制尚不清楚。本研究旨在鉴定参与抑制癌症的 PA 水溶性多肽（PAWPs）中的特定蛋白质，并确定 PAWPs 对小鼠三阴性乳腺癌的影响。在这项研究中，采用 LC-MS 对 105 种 PAWPs 多肽进行肽组学分析，其中 22 种具有潜在的抗肿瘤功能，包括内肽酶抑制剂、金属离子结合蛋白、血管生成抑制剂、细胞间黏附蛋白和细胞外基质修复蛋白。此外，我们表明，PAWPs 经胃内给药可抑制三阴性 4T1 乳腺癌肿瘤的生长和转移。PAWPs 激活了 cleaved-caspase3 的表达，增加了肿瘤细胞凋亡，导致血小板内皮细胞黏附分子（PECAM-1/CD31）表达和血管数量减少，基质金属蛋白酶（MMP）2 和 9 抑制，Cadherin-1（CDH1）/Cadherin-2（CDH2）的比例增加，抑制这些肿瘤中的上皮间质转化（EMT）。因此，PAWPs 可在多个关键部位抑制小鼠三阴性 4T1 乳腺癌的进展和转移，并且含有多种潜在参与这些过程的肿瘤抑制蛋白。
