INHIBITION OF METASTASIS BY CICAPROST IN RATS WITH ESTABLISHED SMT2A MAMMARY-CARCINOMA GROWTH

Cicaprost, a stable prostacyclin analog has been shown to be antimetas tatically active in a series of metastasizing rodent tumors. Whereas s tarting treatment with Cicaprost on the day of tumor implantation was a characteristic feature of our previous investigations, the present s tudy focused on the antimetastatic potency of Cicaprost in animals wit h established tumor growth. We have previously reported that, in Wista r-Furth mts bearing subcutaneously implanted SMT2A mammary carcinoma, Cicaprost fn daily oral doses of 0.1 to 1.0 mg/kg given from the day o f tumor implantation to the end of the experiment led to a strong decr ease in the number of lung metastases. The 1.0 mg/kg doses reduced the number of lung metastases by about 95% compared with the control. In the present study, we have examined the effect of delaying the start o f treatment in animals with established tumor growth. Cicaprost in dai ly oral doses of 0.1 mg/kg given from Day 10 until Day 32 reduced the number of lung metastases by about 80% compared with the control, In c ontrast surgical removal of palpable primary tumors had no effect on l ung metastasis. We conclude that Cicaprost exhibits strong antimetasta tic activity in the SMT2A rat mammary carcinoma model and interferes n ot only with mechanisms of tumor cell-blood cell interaction, tumor ce ll adhesion, and extravasation, but also with steps following extravas ation.