ArticleInternational journal of gastrointestinal cancer2002
The preventive effect of ketoconazole on experimental metastasis from a human pancreatic carcinoma may be related to its effect on prostaglandin synthesis.
Article in International journal of gastrointestinal cancer, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 11 citations in OpenAlex.
- Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer.International journal of molecular medicine · 2019Article
- Review
- Interaction between circulating cancer cells and platelets: clinical implication.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2015Review
- Platelets and cancer: a casual or causal relationship: revisited.Cancer metastasis reviews · 2014Review
- Review
- Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole.Oncogene · 2007Article
- Platelet--cancer interactions: mechanisms and pharmacology of tumour cell-induced platelet aggregation.British journal of pharmacology · 2004Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundArachidonic acid metabolites known to affect platelet function also interfere with tumor growth and metastases. The purpose of this study was to evaluate the anti-metastatic potential of ketoconazole, a thromboxane synthetase and 5-lipoxygenase inhibitor, on hepatic metastasis from a human pancreatic adenocarcinoma in nude mice and its effect on serum prostaglandin levels.
methodsThe human pancreatic tumor cells (RWP-2) were injected intrasplenically in nude mice grouped into control, ketoconazole (270 microg), ketoconazole (360 microg), and ketoconazole (540 microg). The agent was administered intraperitoneally 30 min before and every 24 h after the tumor cell inoculation for 8 days. In a separate experiment thromboxane B2 (TxB2), prostaglandin D2 (PGD2), prostaglandin E2 (PGE2) and 6-Keto-F1a (stable prostacyclin derivative) were measured on blood from controls, tumor bearing animals and animals bearing tumors treated with 270 microg of ketoconazole.
resultsStatistically significant differences were observed between the control and three-treatment groups on the reduction of liver tumor nodules (p < 0.001), and in the liver surface areas occupied by tumor (p < 0.001). The TxB2 levels decreased from 150.6 ng/mL in the tumor bearing to 104.8 ng/mL in the ketoconazole treated animals (p < 0.05). PGD2, PGE2 and 6-keto-F1a levels increased to 7.1 ng/mL, 8.3 ng/mL, and 13.6 ng/mL from 3 ng/mL, 5.8 ng/mL, and 0.02 ng/mL respectively (p < 0.001).
conclusionsThese results indicate that ketoconazole significantly reduced hepatic metastases from the human pancreatic carcinoma RWP-2 in the nude mouse model, and inhibited thromboxane B2 formation, potentiating a concomitant redirection of platelet endoperoxide metabolism into PGD2, PGE2, and 6-keto-F1a. It is hypothesized that the changes in the arachidonic acid metabolism mediate the ameliorating effect of ketoconazole on experimental hepatic metastasis.
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