title: Antitumour effects of Yangzheng Xiaoji in human osteosarcoma: the pivotal role of focal adhesion kinase signalling.
abstract: The present study examined, in vitro and in vivo, the potential antitumour effects of Yangzheng Xiaoji (YZXJ), a traditional Chinese medical formula used in cancer treatment, on osteosarcoma, a tumour type recently found to be sensitive to YZXJ. The human osteosarcoma cell line MG63 was used in cell-matrix adhesion and cell growth assays. The same cell line was used in an in vivo tumour model by establishing subcutaneous osteosarcoma xenografts. Oral and intraperitoneal routes were used to deliver the YZXJ extract. The effect of YZXJ on the activation of focal adhesion kinase (FAK) and paxillin was evaluated by immunofluorescence methods. It was found that YZXJ exhibited a significant inhibitory effect on cell-matrix adhesion as demonstrated by a cell-based assay and electric cell-substrate impedance sensing (ECIS) analysis. The effect was observed together with a reduction in phospho-FAK and phospho-paxillin in the cells when treated with YZXJ. In the in vivo tumour model, YZXJ was found to significantly inhibit the growth of osteosarcoma with a sustained effect observed when YZXJ was delivered intraperitoneally. YZXJ sensitized cells to the effect of FAK inhibitor in vitro and in vivo. It is concluded that Yangzheng Xiaoji plays a significant role in cell-matrix adhesion and tumour growth, likely by inhibiting the activation of the FAK pathway. The therapeutic role of Yangzheng Xiaoji in osteosarcoma warrants further investigation.
authors.affiliation: Cardiff University-Peking University School of Oncology Joint Institute, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Ke
authors.initials: K
authors.lastname: Ji
authors.forename: Fiona
authors.initials: F
authors.lastname: Ruge
authors.forename: Yiling
authors.initials: Y
authors.lastname: Wu
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D004365:Drugs, Chinese Herbal; C496061:PXN protein, human; D051419:Paxillin; D010936:Plant Extracts; C579032:yangzheng xiaoji; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human