인체폐암세포에서 봉독에 의한 prostagladin E2생성 및 telomerase 활성 저하

Abstract

본 연구에서는 봉독의 처리에 따른 A549 폐암세포의 증식억제에서 <TEX>$PGE_2$</TEX> 생성 및 telomerase 활성의 변화 관련성을 조사하였다. A549 세포의 증식은 봉독 처리에 의하여 유의적으로 감소되었으며, 이는 apoptosis 유발과 연관성이 있음을 알 수 있었다. 봉독 처리 농도의 증가에 따라 COX-2의 발현이 전사 및 번역 수준에서 모두 감소되었으며 이에 따른 <TEX>$PGE_2$</TEX>의 생성이 현저하게 감소되었으나, COX-1의 발현에는 큰 변화가 없었다. 또한 봉독 처리에 따라 telomere 조절인자들 중, hTERT, hTR 및 c-myc의 발현이 억제되었으며, telomerase의 활성도 매우 감소되었다. 본 연구의 결과는 <TEX>$PGE_2$</TEX> 생성과 telomerase 활성 저하가 봉독의 항암 작용 표적인자로서 작용될 수 있음을 보여준다. In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin <TEX>$E_2$</TEX> (<TEX>$PGE_2$</TEX>) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in <TEX>$PGE_2$</TEX> synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.