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20(S)-人参皂苷 Rh2 通过调节上皮-间充质转化治疗 LMN-CRC 的应用。

20(S)-ginsenoside Rh2 as agent for the treatment of LMN-CRC via regulating epithelial-mesenchymal transition.

机构信息

Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China.

出版信息

Biosci Rep. 2020 Mar 27;40(3). doi: 10.1042/BSR20191507.

DOI:10.1042/BSR20191507
PMID:32141497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7098129/
Abstract

The lymph node metastasis of colorectal cancer (LMN-CRC) seriously threatens the prognosis of patients. Chemotherapy, as the most common treatment, results in severe bone marrow suppression. 20(S)-ginsenoside Rh2 (SGRh2), a major effective constituent of ginseng, has demonstrated therapeutic effects on a variety of diseases, including some tumours. SGRh2 treatment had no effect on other organs. Therefore, ginsenosides are considered a safe and effective antineoplastic drug. However, the effects of SGRh2 on LMN-CRC remain unknown. The present study investigated the potential effect of SGRh2 on LMN-CRC in vitro and in vivo. SW480 and CoLo205 cell lines were treated with SGRh2. SGRh2 dose-dependently decreased CRC cell proliferation by CCK-8, colony formation and Edu assays. The Transwell and scratch assays revealed that SGRh2 inhibits the migratory and invasive abilities of CRC cells in a dose-dependent manner. Furthermore, the results of Western blotting revealed that SGRh2 decreased the expression of matrix metalloproteinase (MMP)-2 and MMP9. In terms of the underlying mechanisms, SGRh2 regulates CRC metastasis by affecting epithelial-mesenchymal transition (EMT), which significantly up-regulated epithelial biomarkers (E-cadherin) and down-regulated mesenchymal biomarkers (N-cadherin and vimentin) and EMT transcriptional factors (Smad-3, Snail-1, and Twist-1). In vivo, SGRh2 significantly inhibited LMN-CRC without affecting other normal organs. Immunohistochemical results showed that SGRh2 treats LMN-CRC by regulating EMT. These results demonstrate that SGRh2 has therapeutic potential for LMN-CRC.

摘要

结直肠癌的淋巴结转移（LMN-CRC）严重威胁着患者的预后。化疗作为最常见的治疗方法，会导致严重的骨髓抑制。20(S)-人参皂苷 Rh2（SGRh2）是人参的主要有效成分之一，对多种疾病，包括一些肿瘤，都有治疗作用。SGRh2 治疗对其他器官没有影响。因此，人参皂苷被认为是一种安全有效的抗肿瘤药物。然而，SGRh2 对 LMN-CRC 的作用尚不清楚。本研究探讨了 SGRh2 对 LMN-CRC 的体内外潜在作用。用 SGRh2 处理 SW480 和 CoLo205 细胞系。CCK-8、集落形成和 Edu 测定显示 SGRh2 剂量依赖性地降低 CRC 细胞增殖。Transwell 和划痕实验显示 SGRh2 以剂量依赖的方式抑制 CRC 细胞的迁移和侵袭能力。此外，Western blot 结果表明 SGRh2 降低了基质金属蛋白酶（MMP）-2 和 MMP9 的表达。在潜在机制方面，SGRh2 通过影响上皮间质转化（EMT）来调节 CRC 转移，这显著上调上皮生物标志物（E-钙黏蛋白）和下调间充质生物标志物（N-钙黏蛋白和波形蛋白）以及 EMT 转录因子（Smad-3、Snail-1 和 Twist-1）。在体内，SGRh2 显著抑制 LMN-CRC 而不影响其他正常器官。免疫组化结果表明 SGRh2 通过调节 EMT 来治疗 LMN-CRC。这些结果表明 SGRh2 对 LMN-CRC 具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/6b8fe999fd3e/bsr-40-bsr20191507-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/27cf0d614f25/bsr-40-bsr20191507-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/5b1d43cdc2f0/bsr-40-bsr20191507-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/04ebb94a1eec/bsr-40-bsr20191507-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/09675eb81b1b/bsr-40-bsr20191507-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/70bacc67c468/bsr-40-bsr20191507-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/6b8fe999fd3e/bsr-40-bsr20191507-g6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/27cf0d614f25/bsr-40-bsr20191507-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/5b1d43cdc2f0/bsr-40-bsr20191507-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/04ebb94a1eec/bsr-40-bsr20191507-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/09675eb81b1b/bsr-40-bsr20191507-g4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/70bacc67c468/bsr-40-bsr20191507-g5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb19/7098129/6b8fe999fd3e/bsr-40-bsr20191507-g6.jpg

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