ginsenoside-rd and Neoplasm-Metastasis

Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony-forming ability, migration, invasion, and wound-healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse-docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness- and epithelial-mesenchymal transition-related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. Furthermore, ginsenoside Rd significantly decreased the number and size of tumor metastasis nodules in the livers, lungs, and kidneys of mouse model of metastasis. © 2018 IUBMB Life, 71(5):601-610, 2019.

Topics: Animals; Apoptosis; Cell Movement; Cell Proliferation; Colorectal Neoplasms; Epithelial-Mesenchymal Transition; ErbB Receptors; Female; Ginsenosides; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplastic Stem Cells; Signal Transduction; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Metastasis remains a major cause of mortality and poor prognosis in breast cancer patients. Anti-metastatic therapies are in great need to achieve optimal clinical outcome in breast cancer patients. Panax Notoginseng Saponins (PNS) has previously been shown to inhibit breast cancer metastasis in mouse. Here the potential anti-metastatic effect of one of the chemical compounds of PNS, ginsenoside Rd (Rd), was further evaluated in mouse mammary carcinoma 4T1 cells. The results revealed that Rd treatment dose-dependently suppressed cell migration and invasion in cultured 4T1 cells. In 4T1 cell-inoculated mice, Rd treatment led to decreased number of tumor lesions in lungs in both spontaneous and experimental metastasis models. Rd treatment resulted in increased expression of Smad2 in cultured 4T1 cells and in tumors grown from inoculated 4T1 cells. Rd treatment decreased the expression of microRNA (miR)-18a in cultured 4T1 cells and in tumors derived from inoculated 4T1 cells. Smad2 was further verified to be a direct target of miR-18a in 4T1 cells. The significant impact of Rd on counteracting miR-18a-medidated downregulation of Smad2 expression was also demonstrated. Together, the current work shows for the first time that Rd treatment attenuates breast cancer metastasis in part through derepressing miR-18a-mediated Smad2 expression regulation.

Topics: 3' Untranslated Regions; Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Expression Regulation, Neoplastic; Ginsenosides; Humans; Mice; MicroRNAs; Neoplasm Metastasis; RNA Interference; Smad2 Protein; Xenograft Model Antitumor Assays