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

Purpose: We examined whether hyperthermia attenuated the metastatic potential of colon cancer through the induction of heat shock protein 70 (Hsp70).Materials and methods: Colon26 cells were separated into four groups: (1) no pretreatment, (2) hyperthermia at 42°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-κ-B (NF-κ-B) status with and without tumor necrosis factor-α (TNF-α) 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-κ-B by TNF-α 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.