Rodent model of systemic mammary tumor disease by surgical removal of the spontaneously metastasizing SMT2A mammary carcinoma: inhibitory effect of the stable prostacyclin analogue cicaprost on occult metastasis.
Cicaprost, a stable prostacyclin analogue, has been shown to be anti-metastatically active in a series of metastasizing rodent tumors. Start of treatment with cicaprost immediately before tumor implantation was a characteristic feature of our previous investigations. We have reported that in rats bearing mammary-fat-pad-implanted SMT2A mammary carcinoma, cicaprost treatment starting before tumor implantation led to a strong decrease in the number of lung metastases. In order to determine the effect on occult tumor metastasis, the present study examined the effect of starting treatment when tumor metastasis is already present. Cicaprost in daily oral doses of 0.1 mg/kg given from day 10 to day 32 reduced the number of lung metastases by about 75% compared with the control, whereas surgical removal of palpable primary tumors on day 5 or day 10 failed to influence lung metastasis. Using different treatment schedules, a pronounced reduction of the number of lung metastases was achieved by administration of cicaprost until the end of the experiment (from day 5 to day 35), whereas short-term treatments (from day 5 to day 15 or to day 25) were without significant effect. In rats whose SMT2A tumors were surgically removed 10 days after tumor implantation, there was a strong decrease of lung metastases by cicaprost given from day 20 to day 36. In addition to its inhibitory potential in animals with advanced tumor disease, cicaprost showed anti-metastatic action when used in peri-operative treatment of animals whose primary tumors had been removed. In conclusion, the present results demonstrate that cicaprost exhibits strong anti-metastatic activity in the SMT2A rat mammary-carcinoma model with treatment started when occult tumor metastases are already present. Results also indicate that direct effects on tumor cells may contribute to the anti-metastatic action of cicaprost in spontaneously metastasizing tumors.
Schirner
M
M
Research Laboratories, Experimental Oncology, Schering AG, Berlin, Germany.
Schneider
M R
MR
D000273:Adipose Tissue / Q000601:surgery; D000818:Animals; D003131:Combined Modality Therapy; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000601:surgery / Q000628:therapy*; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D051381:Rats; D011920:Rats, Inbred WF
D011464:Epoprostenol; C043867:cicaprost