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Researchers Discover How Low-Dose Aspirin Reduces Cancer Mortality

Both COX-1 and COX-2 appear to be involved

Low-dose aspirin may reduce the risk of cancer metastasis and mortality by inhibiting both cyclooxygenase (COX)-1 and COX-2 pathways, according to data presented at the 13th Annual American Association for Cancer Research (AACR) International Conference on Frontiers in Cancer Prevention Research, held September 28–October 1 in New Orleans, Louisiana.

The involvement of the COX-2 pathway is a new finding, as previous studies suggested that low-dose aspirin lowers the risk of cancer only by inhibiting the COX-1 pathway.

“Studies have shown that aspirin administration for 5 or more years reduces the incidence of all cancers by 38 percent. This benefit is seen even at the low doses of aspirin [e.g., 81 mg daily] required to inhibit platelet aggregation via inhibiting the COX-1 pathway, a finding consistent with the known participation of platelets in the metastatic process,” said lead investigator Pierre Massion, MD, of the Vanderbilt University School of Medicine in Nashville, Tennessee.

In the study, Massion and his colleagues sought to determine whether low-dose aspirin, in addition to blocking platelet function by inhibiting the COX-1 pathway, also reduced levels of the pro-metastatic molecule prostaglandin E2 (PGE2) through inhibition of the COX-2 pathway.

“We found that the potency of low-dose aspirin in inhibiting COX-2 in the tumor cells is as great as or greater than its potency as an inhibitor of COX-1 in the platelet,” Massion said. “This indicates that at a cellular level, aspirin is not selective for the platelet, but could also block COX-2 in cancers.”

“The conventional wisdom held that at low doses, aspirin is selective for the platelet and that it does not block extra-platelet COXs. Thus, the finding that it blocked PGE2 production is likely surprising to most investigators in the field,” Massion added. “Our findings may explain how even a very low dose of aspirin taken daily can produce such a substantial reduction in cancer deaths and metastasis.”

Using three lung adenocarcinoma cell lines, the researchers first found that the doses of aspirin required to inhibit COX-2–dependent PGE2 production were equal to or less than the doses required for the inhibition of COX-1–dependent platelet aggregation.

Next, using urine samples from 54 subjects who received low-dose (81-mg) aspirin tablets for 2 weeks, the researchers demonstrated that aspirin inhibited PGE2 production by 45% and reduced the levels of a metabolite of PGE2, prostacyclin, by 37%.

The researchers also found that by blocking platelet COX-1, aspirin inhibits the adherence of platelets to the cancer cells to prevent metastasis, suggesting that the two mechanisms described act in concert to reduce the risk of cancer mortality.

The study was supported by the National Institutes of Health.

Source: AACR; September 29, 2014.

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