Inhibition of B16 murine melanoma metastasis and enhancement of immunity by fever-range whole body hyperthermia
ABSTRACT
PURPOSE: Whole body hyperthermia (WBH) has been regarded as a promising alternative therapy to cure late stage cancer with metastasis. As the final biological and therapeutic effects are dependent on the specific protocol, the potential of using a microwave-based WBH approach for metastasis inhibition is established and its typical results are discussed.
MATERIALS AND METHODS: The effectiveness of a 30-min whole body hyperthermia (WH) on animals, raised to a rectal temperature of 40.2° ± 0.3°C for 30 min followed by 84 h observation by 2450 MHz microwave irradiation, were evaluated. In an experimental lung metastasis model by injection of B16-F10 melanoma, lungs were removed from sacrificed mice 16 days after tumour implantation, and the expression of heat shock protein, inter-cellular adhesion molecule 1 (ICAM-1), proliferating cell nuclear antigen (PCNA) and cyclin D(1) was examined. CD4(+), CD8(+) and NK cell subpopulation in peripheral blood were measured by flow cytometry before and after the last treatment.
RESULTS: The best therapeutic effect was obtained when the mice were treated with WBH in combination with the initial chemotherapy with cis-diaminodichloroplatinum (CDDP) and dacarbazine (DTIC) (p < 0.05). The WBH alone has an advantage of reduced toxicity and lower cost. Heat shock protein (HSP) expression increased in the hyperthermia groups. Reduction of PCNA and cyclin D(1) was observed in the mice treated with WH alone or in combination with chemotherapy. In the hyperthermia groups, CD4(+)/CD8(+) decreased while the NK increased slightly.
CONCLUSIONS: The whole body hyperthermia protocol described in this work inhibits B16 tumour metastasis by inhibiting cell proliferation, neovascularisation and stimulating favourable immune responses. It demonstrated that WBH treatment benefits therapy of metastasis cancers.