Key result
The combination of dipyridamole and RA-233 reduced hepatic nodules by approximately 70% and tumor surface area by 90% in a nude mouse model of pancreatic cancer metastasis.
Why the study?
Does the combination of dipyridamole and RA-233 prevent human pancreatic cancer cell-induced hepatic metastasis in nude mice?
Does the combination of dipyridamole and RA-233 prevent human pancreatic cancer cell-induced hepatic metastasis in nude mice?
Effect estimate: 70% reduction in hepatic nodules and 90% reduction in surface area
The combination of dipyridamole and RA-233 strongly inhibits tumor cell-induced platelet aggregation and significantly reduces hepatic metastasis in a nude mouse model of pancreatic cancer.
Hypothesis-generating for antiplatelet combinations in pancreatic metastasis; clinical trials needed before human use.
BACKGROUND: Several studies have provided evidence suggesting that platelets play a key role in tumor metastasis. A number of antiplatelet agents have been used to prevent tumor metastasis in animal models and humans. Antiplatelet agents, dipyridamole (adenosine transport inhibitor), and RA-233 (inhibitor of cAMP PDE) were used to prevent tumor-cell-platelet interactions both in in vitro and in vivo systems; however, the data were not very conclusive. METHODS: Our studies used dipyridamole and RA-233 alone and in combination to investigate their effects on human pancreatic tumor cells (RWP-2)-induced platelet aggregation in human blood and on hepatic metastasis in nude mice. To examine effects of dipyridamole and RA-233 on liver metastasis, the tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, dipyridamole (8 mg/kg), RA-233 (8 mg/kg), and dipyridamole plus RA-233 (8 mg/kg each). The agents were administered intraperitoneally 1 hour before and 24 hours after the tumor cell injection. RESULTS: When dipyridamole and RA-233 were used alone, only weak to moderate effects were seen on RWP-2 tumor cell-induced platelet aggregation. However, these agents, when combined, strongly inhibited the tumor cell-induced aggregation in human platelet-rich plasma. In tumor metastasis experiments, reductions of approximately 70% in hepatic nodules and 90% in surface area occupied by the tumor were seen with the combination treatment (dipyridamole plus RA-233) as compared with the control group of mice. CONCLUSIONS: This study suggests that the combination of dipyridamole and RA-233 provides an effective intervention for the antithrombotic approach to the treatment of cancer metastases.
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Tzanakakis et al. (1993) studied Pancreatic cancer metastasis. Dipyridamole plus RA-233 vs. Control, dipyridamole alone, and RA-233 alone was evaluated on Hepatic metastasis (hepatic nodules and surface area occupied by tumor) (70% reduction in hepatic nodules and 90% reduction in surface area). The combination of dipyridamole and RA-233 reduced hepatic nodules by approximately 70% and tumor surface area by 90% in a nude mouse model of pancreatic cancer metastasis.
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