Expression of cyclooxygenase-1 and -2 in cultured human glioma cells of various stages.

ABSTRACT

Cyclooxygenase-1 (COX-1) and -2 (COX-2) are two isoforms of enzymes responsible for the biosynthesis of several forms of prostaglandins (PGs) from arachidonic acid. COX-1 is constitutively expressed in most normal tissues while COX-2 expression is regulated by certain stimuli such as cytokines and growth factors. The expression of COX-2 has been associated with many pathological conditions such as atherosclerosis, inflammation, and cancers (e.g. colon, breast, and lung cancers). COX-2 expression may be associated with the progression of cancers since PGE2, a major product of both isoforms was identified as a tumor-derived immune suppressor. Therefore, the suppression of COX-2 activity using specific COX-2 inhibitors (recently classified non-steroidal anti-inflammatory drugs) may delay the progression of tumors harboring COX-2. The search for tumors that highly express both isoforms of COX serves as a guide to target tumors that are most likely to be susceptible to treatment with specific COX-2 inhibitors. To study a homogeneous population of tumor cells, fifteen samples of primary culture cells were prepared from different human brain tissues and tumors collected from subjects operated on at Siriraj Hospital. Cells were grown to confluent in 75-cm2 tissue culture flask for about 4 weeks. After which time, cells were extracted to evaluate COX-1 and COX-2 protein expressions by immunoblot using specific antibodies. Four out of seven samples of glioblastoma multiforme cells strongly expressed COX-2, while all samples of examined cultured cells expressed COX-1. Cultured cells from astrocytomas had only faint staining for COX-2, while maintaining strong COX-1 expression. Thus COX-2 expression was limited to samples of glioblastoma multiforme, the most advanced stage of astrocytoma. Further study for the suppression of COX-2 activity in inducing tumor apoptosis and in improving cellular immunity against this advanced cancer should be elucidated.