Cyclooxygenase-2 (COX-2) is a potential target for chemotherapy of colorectal cancer (CRC).
In this study, a team of doctors from Leeds, England, tested the antineoplastic activity of the selective COX-2 inhibitor rofecoxib on CRC liver metastases.
The team measured surrogate markers of tumor growth and angiogenesis in a randomized, double-blind, placebo-controlled trial.
They randomized patients undergoing liver resection surgery for metastatic disease to either rofecoxib (25 mg daily) or placebo. The mean duration of rofecoxib therapy was 26 days.
The team measured the apoptosis index (AI; neocytokeratin 18), proliferation index (PI; Ki-67), and microvessel density (MVD; CD31) in the metastases using immunohistochemistry.
They also looked at the effect of rofecoxib on COX-2-positive HCA-7 human CRC cell PGE2 synthesis, proliferation, and apoptosis in vitro.
The researchers found that the rofecoxib-treated metastases had a 29% decrease in MVD, when compared with the placebo-treated tissue.
|Rofecoxib-treated metastases had a 29% decrease in microvessel density.|
However, they found little difference in AI or PI between the 2 groups.
Furthermore, rofecoxib-induced growth arrest and apoptosis of HCA-7 cells occurred only at concentrations significantly higher than the IC50 for COX-2 inhibition.
Dr Stephen Fenwick's team concluded, "Rofecoxib may negatively regulate angiogenesis in human CRC liver metastases".
"The absence of a significant, direct effect of rofecoxib on epithelial cells in liver metastases in vivo mirrors the lack of activity on human CRC cells at pharmacologically relevant concentrations in vitro".