title: Hyperthermia synergizes with tissue factor knockdown to suppress the growth and hepatic metastasis of colorectal cancer in orthotopic tumor model.
abstract: BACKGROUND
  Tissue factor (TF) is a significant risk factor for tumor growth and hepatic metastasis in patients with colorectal cancer (CRC). This study aimed to investigate whether hyperthermia has synergistic anti-tumor effects with TF knockdown in suppressing CRC progression and metastasis in vitro and in vivo.
  
  
  METHODS
  Human colorectal cancer LOVO cells were treated by hyperthermia at 44°C for 2 hr or/and TF siRNA. Then the cells were subjected to colony formation assay. Apoptosis was analyzed by flow cytometry, confocal microscopy, and transmission electron microscopy. The cell migration and invasion abilities were analyzed by wound healing and matrigel assay. In addition, orthotopic nude mice model of CRC was established.
  
  
  RESULTS
  Hyperthermia synergized with TF knockdown to reduce colony formation ability, induce apoptosis, and suppress the migration and invasion of LOVO cells in vitro. Moreover, hyperthermia in combination with TF depletion inhibited the growth and hepatic metastasis of CRC in orthotopic nude mice model. Mechanistically, the synergistic effects were at least partly mediated by inducing JNK mediated apoptosis and suppressing matrix metalloproteinases (MMPs) mediated invasion.
  
  
  CONCLUSIONS
  Hyperthermia in combination with TF-targeted therapy could be a potential approach for CRC treatment.
authors.affiliation: Department of General Surgery, First Hospital of Peking University, Peking University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Mao-Lin
authors.initials: ML
authors.lastname: Tian
authors.forename: Ge
authors.initials: G
authors.lastname: Yu
authors.forename: Yu-Cun
authors.initials: YC
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Ji
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.forename: Yuan-Lian
authors.initials: YL
authors.lastname: Wan
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006979:Hyperthermia, Induced; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D008113:Liver Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000502:physiology; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D013925:Thromboplastin / Q000037:antagonists & inhibitors*
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D013925:Thromboplastin; D048031:JNK Mitogen-Activated Protein Kinases