title: Tiamulin inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of CD73.
abstract: Metastasis is the leading cause of death in breast cancer patients. CD73, also known as ecto-5'-nucleotidase, plays a critical role in cancer development including metastasis. The existing researches indicate that overexpression of CD73 promotes growth and metastasis of breast cancer. Therefore, CD73 inhibitor can offer a promising treatment for breast cancer. Here, we determined whether tiamulin, which was found to inhibit CD73, was able to suppress breast cancer development and explored the related mechanisms.
  
  
  
  We firstly measured the effect of tiamulin hydrogen fumarate (THF) on CD73 using high performance liquid chromatography (HPLC). Then, we investigated cell proliferation, migration and invasion in MDA-MB-231 human breast cancer cell line and 4 T1 mouse breast cancer cell line treated with THF by migration assay, invasion assay and activity assay. Besides, we examined the effect of THF on syngeneic mammary tumors of mice by immunohistochemistry.
  
  
  
  Our data demonstrated that THF inhibited CD73 by decreasing the activity instead of the expression of CD73. In vitro, THF inhibited the proliferation, migration and invasion of MDA-MB-231 and 4 T1 cells by suppressing CD73 activity. In vivo, animal experiments showed that THF treatment resulted in significant reduction in syngeneic tumor growth, microvascular density and lung metastasis rate.
  
  
  
  Our results indicate that THF inhibits growth and metastasis of breast cancer by blocking the activity of CD73, which may offer a promising treatment for breast cancer therapy.
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Shimin
authors.initials: S
authors.lastname: Pei
authors.affiliation: Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.
authors.forename: Huanan
authors.initials: H
authors.lastname: Wang
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
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.identifier: 0000-0003-1326-9861
authors.initials: D
authors.lastname: Lin
mesh_terms: D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology; D005260:Female; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D004224:Diterpenes; D058851:GPI-Linked Proteins; C014224:tiamulin; D015720:5'-Nucleotidase; C548241:NT5E protein, human
keywords: Angiogenesis; Breast cancer; CD73; Metastasis; Thf