Prevention of Lung Metastasis by Intra‐tumoral Injection of Cepharanthin and Staphylococcal Enterotoxin B in Transplantable Rat Osteosarcoma

The antitumor effect of intra‐tumoral injection of Cepharanthin, a biscoclaurin alkaloid extracted from Stephania cephalanta Hayata, and staphylococcal enterotoxin B was evaluated using F344 male rats bearing transplantable rat osteosarcoma, S‐SLM. A macroscopic lung metastatic nodule of tumor was transplanted into the subcutaneous back space, and 0.5 mg of Cepharanthin and 2 pg of staphylococcal enterotoxin B were injected into the tumor on days 12, 13 and 14. On day 28, all animals were killed with an overdose of pentobarbital sodium, and the transplanted tumors and lungs were examined. The wet weight of the lungs of the rats treated with Cepharanthin and staphylococcal enterotoxin B was significantly lower, and apoptosis in the lung metastatic nodules was significantly higher than that of the control or that of rats treated with only Cepharanthin or staphylococcal enterotoxin B. In the transplanted tumors, infiltration of TRAP (tartrate‐resistant acid phosphatase)‐positive multinucleated giant cells was prominent in the rats treated with Cepharanthin and staphylococcal enterotoxin B. These findings indicate that intra‐tumoral injection of Cepharanthin and staphylococcal enterotoxin B induced infiltration of TRAP‐positive multinucleated giant cells within the transplanted rat osteosarcoma, and reduced lung metastasis.