Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry; Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, 350002, China.
Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ, 08854-8020, USA.
Sci Rep. 2017 Jun 20;7(1):3888. doi: 10.1038/s41598-017-02054-y.
Our recent biosystems analysis revealed similarities between embryonic implantation and cancer cell adhesion, which suggests that abortifacients may be good for safe and effective metastatic chemoprevention targeting circulating tumor cells (CTC). Here we test the hypothesis by using the well-known abortion herb Achyranthes bidentata Blume (A. bidentata). Five compounds were separated from the herb root. Among them, ginsenoside Ro was the most potent in inhibiting embryonic implantation within non-cytotoxic concentrations. It specifically inhibited the metastatic dissemination capability of colon cancer cells HT29, including the migration and invasion ability, and their adhesion to human endothelium through inhibiting integrin αvβ6, MMP-2, MMP-9, and ERK phosphorylation by HT29. Pretreatment of nude mice with oral ginsenoside Ro followed by HT29 intravenous inoculation and 40-day oral ginsenoside Ro significantly prevented lung metastasis with downregulation of integrin αvβ6 and no toxicity. The present study firstly introduces the new conception of utilizing safe and effective abortion botanic medicines for CTC-based metastatic chemoprevention.
我们最近的生物系统分析揭示了胚胎着床和癌细胞黏附之间的相似性,这表明流产药可能是一种安全有效的针对循环肿瘤细胞(CTC)的转移性化学预防药物。在这里,我们通过使用著名的堕胎草药牛膝(Achyranthes bidentata Blume,A. bidentata)来验证这一假说。从草药根部分离出了五种化合物。其中,人参皂苷 Ro 在非细胞毒性浓度下抑制胚胎着床的能力最强。它通过抑制整合素 αvβ6、MMP-2、MMP-9 和 ERK 磷酸化,特异性抑制结肠癌 HT29 细胞的转移扩散能力,包括迁移和侵袭能力,以及它们与人内皮细胞的黏附。通过口服人参皂苷 Ro 预处理裸鼠,然后静脉注射 HT29 并口服人参皂苷 Ro40 天,可显著抑制肺转移,同时下调整合素 αvβ6,且无毒性。本研究首次提出了利用安全有效的堕胎植物药进行基于 CTC 的转移性化学预防的新概念。