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

Abstract

Several studies have shown that the Kampo medicine Juzen-taiho-to (Si-Quan-Da-Bu-Tang in Chinese) has various biological activities, including anti-tumor effects when combined with surgical excision or with chemotherapeutic drugs. Here we investigated the effect of combined therapy with interferon (IFN)-alpha A/D and Juzen-taiho-to on experimental lung metastasis of murine renal cell carcinoma (Renca) cells. Five consecutive administrations of IFN-alpha A/D to Renca-bearing mice resulted in dose-dependent inhibition of lung metastasis. IFN-alpha A/D at the dose of 100,000 IU/mouse significantly inhibited the metastasis, but a marked loss of body weight was observed during and after the administration. In contrast, oral administration of Juzen-taiho-to (50 mg/mouse) alone tended to inhibit the metastasis, but the effect was not statistically significant. The combination treatment of suboptimal doses of IFN-alpha A/D and Juzen-taiho-to markedly augmented the antimetastatic effect without causing any loss of body weight, as compared with either treatment alone. Similar results were also obtained by treatment with IFN-gamma in combination with Juzen-taiho-to. Clinically, immunotherapy with IFNs has been primarily approved for the treatment of patients with metastatic renal cell carcinoma, but sufficient efficacy has not yet been obtained. Therefore, the combination of IFNs with Juzen-taiho-to may provide a means to increase the therapeutic potential of IFNs and to decrease their toxicity for the treatment of metastatic renal cell carcinoma.