title: Ulinastatin exerts synergistic effects with taxotere and inhibits invasion and metastasis of breast cancer by blocking angiogenesis and the epithelial-mesenchymal transition.
abstract: Urinary trypsin inhibitor (UTI) ulinastatin as a broad-spectrum protease inhibitor has been widely used to treat acute pancreatitis and shock and to improve the surgical outcome in the clinic. In the present study, we investigated the potential antihuman breast cancer effects of UTI and its combination with taxotere (TXT). Human primary breast cancer cells and breast cancer cell line MDA-MB-231 cells were treated with UTI with or without TXT, and invasion and metastasis ability of these cells were evaluated, respectively, by a transwell assay. Reverse transcription-polymerase chain reaction was used to detect fibroblast growth factor, vascular endothelial growth factor c, epidermal growth factor, epidermal growth factor receptor, transforming growth factor-β1, and protein kinase B/AKT. We also investigated the in vivo role of UTI by using a xenograft mouse model, and immunohistochemical assay was employed to show the expression of factors involved in either angiogenesis or the epithelial-mesenchymal transition (EMT). Our results showed that UTI inhibited invasion and metastasis in both primary and MDA-MB-231 cells both in vivo and in vitro. Especially, UTI presented the significant combined effects with TXT on these cells in terms of angiogenesis blocking and EMT inhibition. These results suggest that UTI and its combination with TXT present therapeutic potential against breast cancer and deserve further preclinical and clinical studies.
authors.affiliation: Department of Breast and Thyroid, The Second Affiliated Hospital, Chongqing University of Medical Sciences, Chongqing 400010, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Sun
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Biao
authors.initials: B
authors.lastname: Zhong
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D006023:Glycoproteins; D043823:Taxoids; D014361:Trypsin Inhibitors; D000077143:Docetaxel; C028665:urinastatin