title: Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and -2.
abstract: BACKGROUND
  Metastasis is the major cause of death in breast cancers. MMPs play a key role in tumor microenvironment that facilitates metastasis. The existing researches suggest that the high expression of gelatinase A and B (MMP2 and MMP9) promote the metastasis of breast cancer. Therefore, gelatinase inhibitor can effectively suppress tumor metastasis. However, at present, there is no dramatically effective gelatinase inhibitor against breast cancer.
  
  
  METHODS
  We screened gelatinase inhibitor among Chinese herbal medicine by molecular docking technology; investigated the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line in response to the treatment with the screened inhibitor by wound assay, invasion assay and gelatin zymography; then further examined the effects of inhibitor on allograft mammary tumors of mice by immunohistochemistry.
  
  
  RESULTS
  We successfully screened an Chinese herbal medicine-Plantamajoside(PMS)-which can reduce the gelatinase activity of MMP9 and MMP2. In vitro, PMS can inhibit the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line by decreasing MMP9 and MMP2 activity. In vivo, oral administration of PMS to the mice bearing 4T1 cells induced tumors resulted in significant reduction in allograft tumor volume and weights, significant decrease in microvascular density and significant lower lung metastasis rate.
  
  
  CONCLUSIONS
  Our results indicate that as a promising anti-cancer agent, PMS may inhibit growth and metastasis of breast cancer by inhibiting the activity of MMP9 and MMP2.
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. s11040604@cau.edu.cn.
authors.forename: Shimin
authors.initials: S
authors.lastname: Pei
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. wwwyangxu@163.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China. whn868@163.com.
authors.forename: Huanan
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. 1036354181@qq.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. cauzhoubin@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. dzhangdvm@cau.edu.cn.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China. csama@sina.com.
authors.forename: Degui
authors.initials: D
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002396:Catechols / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000473:pathology; D008517:Phytotherapy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D002396:Catechols; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D061965:Matrix Metalloproteinase Inhibitors; C421173:plantamajoside; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9