Effect of interferon-alpha A/D in combination with the Japanese and Chinese traditional herbal medicine Juzen-taiho-to on lung metastasis of murine renal cell carcinoma

Several studies have shown that the Kampo medicine Juzen-taiho-to (Si-Quan- Da-Bu-Tang in Chinese) has various biological activities, including anti-tu mor effects when combined with surgical excision ol with chemotherapeutic d rugs. Here we investigated the effect of combined therapy with interferon ( IFN)-alpha AID and Juzen-taiho-to on experimental lung metastasis of murine renal cell carcinoma (Renca) cells. Five consecutive administrations of IF N-alpha A/D to Renca-bearing mice resulted in dose-dependent inhibition of lung metastasis. IFN-alpha AID at the dose of 100,000 IU/mouse significantl y inhibited the metastasis, but a marked loss of body weight was observed d uring and after the administration. In contrast oral administration of Juze n-taiho-to (50 mg/mouse) alone tended to inhibit the metastasis, but the ef fect was not statistically significant. The combination treatment of subopt imal doses of IFN-alpha AID and Juzen-taiho-to markedly augmented the antim etastatic effect without causing any loss of body weight, as compared with either treatment alone. Similar results were also obtained by treatment wit h IFN-gamma in combination with Juzen-taiho-to. Clinically, immunotherapy w ith IFNs has been primarily approved for. the treatment of patients with me tastatic renal cell carcinoma, but sufficient efficacy has not yet been obt ained. Therefore, the combination of IFNs with Juzen-taiho-to may provide a means to ina ease the therapeutic potential of IFNs and to decrease their toxicity for the treatment of metastatic renal cell carcinoma.