Characteristics of the Inhibitory Effect of Mitoxantrone and Pirarubicin on Lung Metastases of Colon Carcinoma 26

This study was performed to evaluate the antimetastatic activity of antitumor agents against metastatic colon carcinoma 26 (Co 26Lu), and to investigate their mechanisms of action. Pirarubicin demonstrated the most striking antitumor activity in mice bearing intravenously injected Co 26Lu cells. Etoposide and mitoxantrone also showed marked antitumor activity. Pirarubicin and mitoxantrone also exerted remarkable inhibitory effect on spontaneous lung metastases from subcutaneously implanted Co 26Lu. Pirarubicin showed marked inhibition of both primary tumor growth and lung metastases. Mitoxantrone was effective in preventing lung metastases even at doses that did not exhibit an antitumor effect on the primary tumor. Moreover, mitoxantrone administered two days after intravenous injection of tumor cells obviously reduced the number of lung colonies, while simultaneous injection of the drug did not inhibit colony formation. Mitoxantrone effectively inhibited angiogenesis on the chorioallantoic membrane at doses that did not affect the growth rate of embryos. These results suggest that mitoxantrone, besides its direct antitumor effect on tumor cells, may inhibit lung metastases by inhibiting angiogenesis.