title: Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with U937 cells.
abstract: OBJECTIVE
  Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice.
  
  
  RESULTS
  Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression.
  
  
  CONCLUSIONS
  TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells.
  
  
  CONCLUSIONS
  TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Cheng-Yu
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Division of Anatomic Pathology, Taipei Tzu Chi Hospital, Taipei, Taiwan.
authors.forename: Chih-Kung
authors.initials: CK
authors.lastname: Lin
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Gu-Jiun
authors.initials: GJ
authors.lastname: Lin
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Cheng-Chih
authors.initials: CC
authors.lastname: Hsieh
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan.|Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.affiliation: School of Dentistry, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Shing
authors.initials: YS
authors.lastname: Shieh
authors.affiliation: Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. h6183@yahoo.com.tw.|School of Dentistry, National Defense Medical Center, Taipei, Taiwan. h6183@yahoo.com.tw.|Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei, Taiwan. h6183@yahoo.com.tw.|Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, No. 161, Section 6, Min-Chuan East Road, Neihu 114, Taipei 114, Taiwan, People's Republic of China. h6183@yahoo.com.tw.
authors.forename: Yuan-Wu
authors.initials: YW
authors.lastname: Chen
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004852:Epoxy Compounds / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010616:Phenanthrenes / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D059016:Tumor Microenvironment; D020298:U937 Cells
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016207:Cytokines; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide
keywords: Chemoprevention; Co-inoculate; Oral cancer cell; Triptolide; U937 cell