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Effects of prostacyclin analogues in in vivo tumor models
M R Schneider1, E Schillinger, M Schirner
1Research Laboratories of Schering AG Berlin/Bergkamen West Germany.
Abstract:
Much attention has recently focused on the role of tumor cell-platelet interaction in the metastatic cascade. Prostacyclin and stable prostacyclin analogues have been shown to inhibit specifically the formation of metastases in experimental tumor models. This action is based on their ability to reduce the attachment of tumor cells to platelets and to inhibit adhesion of tumor cells-platelet aggregates to the endothelial lining. To investigate the antimetastatic potential of two prostacyclin analogues (Iloprost and Eptaloprost, Schering AG), we have tested these compounds in the spontaneously metastasizing R 3327 MAT Lu prostate carcinoma of the Cop rat in two types of experiments. Treatment was performed for 33 days, starting one day before s.c. implantation of the tumor. The primary s.c.-implanted tumor remained in situ throughout the experiment. In the first test, Iloprost (0.3 micrograms/kg/min) and Eptaloprost (0.1 micrograms/kg/min) were administered via Alzet mini pumps s.c.. There was a considerable reduction of the number of visible lung metastases by Eptaloprost. In the second test, Eptaloprost was administered p.o. in doses of 0.1 and 0.5 mg/kg daily. The number of lung metastases was significantly reduced. Both compounds had no effect on the growth of the primary tumor in the first as well as in the second test. These data show that the prostacyclin analogue Eptaloprost has a significant antimetastatic activity in a spontaneously metastasizing tumor model and thus merits further investigation.
Insights
Prostacyclin analogues like Eptaloprost show significant antimetastatic activity by reducing tumor cell-platelet interactions. Eptaloprost effectively decreased lung metastases in a prostate cancer model without impacting primary tumor growth.
Area of Science:
- Oncology
- Pharmacology
- Cancer Metastasis Research
Background:
- Tumor cell-platelet interactions are crucial in cancer metastasis.
- Prostacyclin and its analogues can inhibit metastasis formation in experimental models.
- These compounds reduce tumor cell attachment to platelets and endothelial lining.
Purpose of the Study:
- To investigate the antimetastatic potential of Iloprost and Eptaloprost.
- To evaluate these prostacyclin analogues in a spontaneously metastasizing prostate carcinoma model (R 3327 MAT Lu).
Main Methods:
- Two experimental tests were conducted over 33 days, starting before tumor implantation.
- Iloprost and Eptaloprost were administered via subcutaneous mini pumps and orally.
- The primary tumor remained in situ throughout the experiments, with lung metastases quantified.
Main Results:
- Eptaloprost significantly reduced the number of visible lung metastases in both administration routes.
- Iloprost also showed a considerable reduction in lung metastases when administered via mini pumps.
- Neither compound affected the growth of the primary subcutaneous tumor.
Conclusions:
- The prostacyclin analogue Eptaloprost demonstrates significant antimetastatic activity.
- Eptaloprost's efficacy in a spontaneously metastasizing model warrants further investigation for cancer treatment strategies.