title: Antitumor effect of pretreatment for colon cancer cells with hyperthermia plus geranylgeranylacetone in experimental metastasis models and a subcutaneous tumor model of colon cancer in mice.
abstract: OBJECTIVE
  We examined whether hyperthermia attenuated the metastatic potential of colon cancer through the induction of heat shock protein 70 (Hsp70).
  
  
  METHODS
  Colon26 cells were separated into four groups: (1) no pretreatment, (2) hyperthermia at 42 degrees C for 1 hour, (3) pretreatment with geranylgeranylacetone (GGA) 10(-6) M for 2 hours, and (4) hyperthermia after GGA treatment. We measured cell viabilities and the contents of Hsp70. We assessed nuclear factor-kappa-B (NF-kappa-B) status with and without tumor necrosis factor-alpha (TNF-alpha) stimulation. For in vivo study, colon26 cells were injected via the tail vein or into a subcutaneous area of mice and the numbers of lung metastatic nodules or the volumes of subcutaneous tumors were assessed. Untreated cells were incubated with PKH26. Experimental metastasis models were then generated and used to assess the fixed cancer cells.
  
  
  RESULTS
  Tumor development in the subcutaneous tumor models and cell viabilities were similar among the four groups. However, the GGA plus hyperthermia group had fewer lung metastatic nodules in the experimental lung metastasis model and higher Hsp70 induction than the other cell groups. The GGA plus hyperthermia pretreatment group also showed a lower number of fixed cells in lungs and lower activation of NF-kappa-B by TNF-alpha than the other cell groups.
  
  
  CONCLUSIONS
  It is suggested the metastatic potential but not the proliferation potency of cancer cells is inhibited by the transient induction of Hsp70.
authors.affiliation: Department of Inflammation and Immunology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Okayama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Satoko
authors.initials: S
authors.lastname: Adachi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hattori
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa