Local Radiofrequency Hyperthermia Inhibits the Growth of Primary Tumors and Lung Metastases in a 4T1/luc Murine Breast Cancer Model

• Published in: Thermal Medicine Vol. 26; no. 1; pp. 19 - 29
• Main Authors: KOJIMA, KIYOHIDE, MIZUTANI, JUN, OTSUKA, TAKANOBU, OKADA, HIDECHIKA, FURUYA, AIHARU, ISHIGURO, MASAE, WAGURI-NAGAYA, YUKO
• Format: Journal Article
• Language: Japanese
• Published: Japanese Society for Thermal Medicine 2010
• Subjects: breast cancer cell line; metastases; mouse model; natural killer cells; radiofrequency hyperthermia
• ISSN: 1882-2576; 1882-3750
• DOI: 10.3191/thermalmed.26.19

Radiofrequency hyperthermia has been widely and successfully used for treatment of malignant tumors. Metastatic tumors are suppressed in some patients harboring malignant tumors during primary tumor treatment with hyperthermia. In the present study, regression of tumor size and visceral metastases were investigated in a mouse model involving treatment with local radiofrequency hyperthermia. 4T1/luc murine breast cancer cells were subcutaneously transplanted into the left thighs of female BALB/c mice. When the primary tumors reached a mean diameter of 5 mm, the tumors were treated with local 8 MHz radiofrequency hyperthermia two times a week for 3 weeks ; control animals were not treated with hyperthermia. In another group of mice, primary tumors were treated with doxorubicin injected into the tumor on day 7 after the tumor transplant, and were not treated with radiofrequency hyperthermia. The diameters of the primary tumors, the number of microscopic visceral metastasic foci, and luciferase activity in viscera were measured, and the results were compared between the groups of animals. Splenic lymphocytes were also examined using flow cytometry. Primary tumor growth was suppressed by both local radiofrequency hyperthermia and by intratumoral doxorubicin injection. However, lung metastases were inhibited only by local radiofrequency hyperthermia as shown by microscopic evaluation and luciferase activity assays. Liver metastases were not detected in any mice. The overall survival time was prolonged by local radiofrequency hyperthermia. The number of natural killer cells in the spleen was significantly increased after treatment with local radiofrequency hyperthermia, and this increase in natural killer cells in the spleen might account for the inhibition of lung metastases. In conclusion, primary tumor growth and the frequency of lung metastases were reduced by local radiofrequency hyperthermia treatments in the 4T1/luc mouse model.