Antitumor effect of whole body hyperthermia with alpha-galactosylceramide in a subcutaneous tumor model of colon cancer
ABSTRACT
AIM: Whole body hyperthermia (WBH) has been used clinically as an adjunct to radio- and chemotherapy in patients with various cancers. Recently, it has been reported that an activation of the immune system has recently been reported as a possible contributor to the therapeutic effects of WBH. Conversely, the glycolipid alpha-galactosylceramide (alpha-GalCer) is recognized by natural killer (NK) T cells together with the monomorphic MHC-like antigen, CD1d, in mice and humans. This study investigated the antitumor effects of WBH combined with alpha-GalCer in a mouse subcutaneous tumor model of colon cancer.
METHODS: Colon26 cells were inoculated subcutaneously into male BALB/c mice to establish subcutaneous tumor. Colon26-bearing mice were treated with WBH using far infrared rays three times/week. Rectal temperature was maintained for 60 min at 41 degrees C. In some experimental groups, alpha-GalCer was intraperitoneally injected before WBH. We investigated the therapeutic effects of WBH, alpha-GalCer and combined therapy.
RESULTS: (1) Compared with controls, WBH alone resulted in significant inhibition of tumor growth. (2) No inhibitory effect on tumor growth was seen with alpha-GalCer. (3) The combination of WBH and alpha-GalCer showed significant inhibition of tumor growth and prolongation of survival. (4) Serum IFN-gamma increased after 3 h and returned to basal levels by 24 h after alpha-GalCer administration. (5) CTL activity was enhanced following combination therapy with WBH and alpha-GalCer.
CONCLUSION: WBH showed antitumor effects in a mouse subcutaneous tumor model of colon cancer. Addition of alpha-GalCer increased the efficacy of WBH, probably via enhancement of immune response.