title: Ginsenoside Rd attenuates breast cancer metastasis implicating derepressing microRNA-18a-regulated Smad2 expression.
abstract: 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.
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Peiwei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Du
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Minqi
authors.initials: M
authors.lastname: Xiong
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Jingang
authors.initials: J
authors.lastname: Cui
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Qinbo
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Wang
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Yueyang Hospital &Clinical Research Institute of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis; D034622:RNA Interference; D051899:Smad2 Protein / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides; C581632:MIRN18 microRNA, human; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein; C049863:ginsenoside Rd