title: A novel biphenyl urea derivate inhibits the invasion of breast cancer through the modulation of CXCR4.
abstract: The increased migration and invasion of breast carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. CXCR4, the receptor for stromal-derived factor-1, is reportedly involved in breast carcinogenesis and invasion. In this study, we investigated a novel biphenyl urea derivate, TPD7 for its ability to affect CXCR4 expression as well as function in breast cancer cells. We demonstrated that TPD7 inhibited the breast cancer proliferation and down-regulated the CXCR4 expression on breast cancer cells both over-expressing and low-expressing HER2, an oncogene known to induce the chemokine receptor. Treatments with pharmacological proteasome inhibitors partial suppressed TPD7-induced decrease in CXCR4 expression. Real-time PCR analysis revealed that down-regulation of CXCR4 by TPD7 also occurred at the translational level. Inhibition of CXCR4 expression by TPD7 further correlated with the suppression of SDF-1α-induced migration and invasion in breast tumour cells, knockdown of CXCR4 attenuated TPD7-inhibitory effects. In addition, TPD7 treatment significantly suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression, the downstream targets of CXCR4, perhaps via inactivation of the ERK signaling pathway. Overall, our results showed that TPD7 exerted its anti-invasive effect through the down-regulation of CXCR4 expression and thus had the potential for the treatment of breast cancer.
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Yingzhuan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
authors.forename: Langchong
authors.initials: L
authors.lastname: He
mesh_terms: D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002224:Carbanilides / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006898:Hydroxylamines / Q000737:chemistry / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay
chemical_list: D001713:Biphenyl Compounds; D002224:Carbanilides; D054377:Chemokine CXCL12; D006898:Hydroxylamines; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; C000604982:TPD7 compound; C010574:biphenyl
keywords: CXCR4; biphenyl urea derivate; breast cancer; invasion