Department of Breast Surgery (Integrated Traditional and Western Medicine), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China.
The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.
J Ethnopharmacol. 2018 Jan 30;211:89-100. doi: 10.1016/j.jep.2017.09.033. Epub 2017 Sep 27.
Triple-negative breast cancer (TNBC) often presents with a high histological grade and high malignancy, which greatly contribute to patient morbidity and mortality. Rhizoma Amorphophalli exhibits many biological and pharmacological activities, but its potential as a therapeutic agent for the treatment of metastatic TNBC patients remains poorly understood.
The aim of this study was to determine whether Rhizoma Amorphophalli inhibits metastasis in the human TNBC MDA-MB-231 cell line.
CCK-8 and colony formation assays were adopted for the analysis of cell activity and cell proliferation, respectively. Flow cytometry was used for cell cycle analysis. Wound healing and transwell assays were performed to assess cell migration and invasion, respectively. PI3K/Akt/mTOR signaling pathways were analyzed through western blotting. Breast cancer cell metastasis to the lung in a xenograft model was evaluated by in vivo fluorescence imaging. A GC-MS analysis was performed to determine the main components of the petroleum ether fraction from the ethanol extract of Rhizoma Amorphophalli (abbreviated RhA).
RhA significantly reduced breast cancer cell viability and proliferation. The flow cytometry analysis indicated that RhA induced MDA-MB-231 cell arrest at the S phase. Additionally, RhA decreased MDA-MB-231 cell migration and invasion and inhibited the PI3K/Akt/mTOR signaling pathway. In addition, mice treated with RhA exhibited a significant reduction in tumor infiltration and a decrease in breast cancer cell metastasis to the lung. The GC-MS analysis results showed that RhA contained a large number of unsaturated fatty acids, such as octadecadienoic acid (linoleic acid), octadecatrienoic acid (linolenic acid), and oleate, which might represent the anticancer components of the extract.
The results of this study suggest that RhA has potential as a therapeutic candidate for metastatic TNBC treatment.
三阴性乳腺癌（TNBC）常表现为高组织学分级和高恶性程度，这极大地导致了患者的发病率和死亡率。魔芋根茎表现出许多生物和药理学活性，但作为转移性 TNBC 患者治疗药物的潜力仍知之甚少。
本研究旨在确定魔芋根茎是否能抑制人 TNBC MDA-MB-231 细胞系的转移。
采用 CCK-8 和集落形成实验分别分析细胞活性和细胞增殖，采用流式细胞术分析细胞周期。通过划痕愈合和 Transwell 实验分别评估细胞迁移和侵袭，采用 Western blot 分析 PI3K/Akt/mTOR 信号通路。通过体内荧光成像评估乳腺癌细胞在异种移植模型中向肺部的转移。采用 GC-MS 分析测定魔芋根茎乙醇提取物石油醚部分的主要成分（简称 RhA）。
RhA 显著降低乳腺癌细胞活力和增殖。流式细胞术分析表明 RhA 诱导 MDA-MB-231 细胞停滞在 S 期。此外，RhA 降低 MDA-MB-231 细胞迁移和侵袭，并抑制 PI3K/Akt/mTOR 信号通路。此外，用 RhA 处理的小鼠表现出肿瘤浸润显著减少和乳腺癌细胞向肺部转移减少。GC-MS 分析结果表明，RhA 含有大量不饱和脂肪酸，如十八碳二烯酸（亚油酸）、十八碳三烯酸（亚麻酸）和油酸，这些可能是提取物的抗癌成分。
本研究结果表明，RhA 可能作为转移性 TNBC 治疗的候选治疗药物。
