Meta-analyses have demonstrated that low-dose
aspirin reduces the risk of developing
adenocarcinoma metastasis, and when
colon cancer is detected during
aspirin treatment, there is a remarkable 83% reduction in risk of
metastasis. As platelets participate in the metastatic process, the antiplatelet action of low-dose
aspirin likely contributes to its antimetastatic effect. Cycloxooxygenase-2 (COX-2)-derived
prostaglandin E2 (
PGE2) also contributes to
metastasis, and we addressed the hypothesis that low-dose
aspirin also inhibits
PGE2 biosynthesis. We show that low-dose
aspirin inhibits systemic
PGE2 biosynthesis by 45% in healthy volunteers (P < 0.0001).
Aspirin is found to be more potent in
colon adenocarcinoma cells than in the platelet, and in
lung adenocarcinoma cells, its inhibition is equivalent to that in the platelet. Inhibition of COX by
aspirin in
colon cancer cells is in the context of the
metastasis of
colon cancer primarily to the liver, the organ exposed to the same high concentrations of
aspirin as the platelet. We find that the interaction of activated platelets with
lung adenocarcinoma cells upregulates COX-2 expression and
PGE2 biosynthesis, and inhibition of platelet COX-1 by
aspirin inhibits
PGE2 production by the platelet-
tumor cell aggregates. In conclusion, low-dose
aspirin has a significant effect on extraplatelet
cyclooxygenase and potently inhibits COX-2 in lung and
colon adenocarcinoma cells. This supports a hypothesis that the remarkable prevention of
metastasis from
adenocarcinomas, and particularly from
colon adenocarcinomas, by low-dose
aspirin results from its effect on platelet COX-1 combined with inhibition of
PGE2 biosynthesis in metastasizing
tumor cells.
Cancer Prev Res; 9(11); 855-65. ©2016 AACR.