The antitumor effect of postoperative treatment with genistein alone or combined with cyclophosphamide in mice bearing transplantable tumors.

Genistein has been shown to be an inhibitor of tumor growth as well in vitro as in vivo. In addition to its antitumor effect, genistein reveals the antimetastatic and antiangiogenic properties. In this paper we described the results of our studies on the antimetastatic activity of genistein alone or combined with cyclophosphamide (CY) in mice which before this treatment were exposed to surgical excision of the primary tumor. Three transplantable subcutaneously growing mouse tumors were applied: Lewis lung cancer (LL2), B16F-10 melanoma and 16/C mammary cancer. The antitumor and antimetastatic effect was evaluated by the estimation of a number of lung colonies and a number of primary tumor recurrence as compared to the control mice exposed to the s.c. tumor extirpation only. Twenty days after the surgery, an average of 52 lung tumor colonies per mouse were detected in control mice bearing LL2 cancer. The treatment with genistein resulted in the reduction of the lung colonies to 24 per mouse. The treatment with CY reduced the number of lung colonies to 12 (p < 0.05) and combined treatment with both agents to 4 (p < 0.05). The percentage of primary tumor recurrence was 25, 86, 67 and 80% in the control, genistein treated, CY treated, and genistein + CY treated mice, respectively. Twenty days after the surgery, no lung metastases in the control mice bearing B16F-10 melanoma were observed. The percentage of primary tumor recurrence in the control, genistein treated, CY treated and genistein + CY treated mice was: 86, 29, 57 and 67% respectively. Two different protocols of the treatment with genistein were applied in 16/C mammary cancer model. In the first one genistein was injected before and in the other after surgical excision of tumor. The histological examination revealed the presence of lung metastases in all, untreated and treated, according to both protocols groups of mice. The percentage of primary tumor recurrence in the control mice, genistein treated according to the protocol I, and II was: 100, 40, and 40%, respectively.