Inhibition of hepatic metastasis from a human pancreatic adenocarcinoma (RWP‐2) in the nude mouse by prostacyclin, forskolin, and ketoconazole

Abstract

Metastasis is a multistep phenomenon in which platelets appear to play an important role. This study examined several compounds for their effects on experimental hepatic metastasis and on human pancreatic tumor cell‐platelet interactions. Prostacyclin (PGI2) and forskolin (stimulators of platelet adenylate cyclase) and ketoconazole (inhibitor of lipoxygenese and thromboxane synthetase) were used in order to investigate their effects on hepatic metastases from a human pancreatic tumor cell (RWP‐2) in the nude mouse. The tumor cells were injected intrasplenically and the animals were divided into control, prostacyclin (PGI2 200 μg), forskolin (150 μg), and ketoconazole (180 μg) groups. All three drugs were administered intraperitoneally 30 minutes before and 24 hours after the tumor cell injections. Statistically significant differences were observed between control and treated groups in tumor surface area (P < 0.001), percentage of liver surface area occupied by tumor (P < 0.001), and number of tumor colonies (P < 0.004 for prostacyclin, P < 0.005 for forskolin, and P < 0.001 for ketoconazole). These agents also strongly inhibited RWP‐2‐induced platelet aggregation in human platelet‐rich plasma. Copyright © 1990 American Cancer Society