Department of Breast Surgery (Integrated Traditional and Western Medicine), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai 200032, China.
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
J Ethnopharmacol. 2019 May 10;235:206-218. doi: 10.1016/j.jep.2019.02.004. Epub 2019 Feb 4.
Amorphophalli Rhizoma has been widely used as an adjuvant treatment for advanced or metastatic breast cancer, pancreatic cancer, hepatoma, and malignant lymphoma, but its molecular mechanism of action for treatment of metastatic triple-negative breast cancer (TNBC) is generally poorly understood.
To investigate genomic changes related to the inhibitory effect of Amorphophalli Rhizoma and to elucidate the molecular mechanism of this inhibition in MDA-MB-231 TNBC cells.
Gene chip analysis was employed to explore genomic changes caused by Amorphophalli Rhizoma in TNBC cells. Potential classical signaling pathways, upstream regulators, functions, regulatory effects and gene interaction networks were analyzed by Ingenuity Pathway Analysis (IPA). Real-time quantitative PCR (RT-qPCR) and RNA interference (RNAi) assays were used to clarify the roles of potential target genes.
In total, 536 significantly upregulated and 648 significantly downregulated genes were identified between the group treated with Amorphophalli Rhizoma extract and that treated with vehicle. Many of these differentially expressed genes (DEGs) in TNBC cells are involved in DNA replication, recombination and repair, the cell cycle, and cellular assembly and organization. Attenuation of KNL1, OLFML2A, RTKN2 and SGO1 gene expression by Amorphophalli Rhizoma significantly induced cell cycle arrest and suppressed cell proliferation and migration.
The inhibitory effects of Amorphophalli Rhizoma in TNBC cells likely occur through regulation of the spindle checkpoint, chromosomal and centrosomal instability, and cell membrane stability.
魔芋根茎已被广泛用于辅助治疗晚期或转移性乳腺癌、胰腺癌、肝癌和恶性淋巴瘤，但它在治疗转移性三阴性乳腺癌（TNBC）方面的作用机制在很大程度上尚未被了解。
研究与魔芋根茎抑制作用相关的基因组变化，并阐明其在 MDA-MB-231 TNBC 细胞中的分子抑制机制。
采用基因芯片分析方法探讨魔芋根茎对 TNBC 细胞基因组变化的影响。通过 Ingenuity Pathway Analysis（IPA）分析潜在的经典信号通路、上游调节剂、功能、调控作用和基因相互作用网络。实时定量 PCR（RT-qPCR）和 RNA 干扰（RNAi）实验用于阐明潜在靶基因的作用。
共鉴定出魔芋根茎提取物处理组与溶剂处理组之间有 536 个显著上调和 648 个显著下调的基因。这些在 TNBC 细胞中差异表达的基因（DEGs）中有许多涉及 DNA 复制、重组和修复、细胞周期以及细胞组装和组织。魔芋根茎对 KNL1、OLFML2A、RTKN2 和 SGO1 基因表达的抑制作用显著诱导细胞周期停滞，并抑制细胞增殖和迁移。
魔芋根茎对 TNBC 细胞的抑制作用可能是通过调节纺锤体检查点、染色体和中心体不稳定以及细胞膜稳定性来实现的。
