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및 문제점지금까지의 연구를 종합하면 COX-2가 종양 발생에 깊이 관여하고 있음은 명확한 사실이다 . 그러나 아직 해결해야 할 문제가 많은 것도 사실이다 . 즉, COX-2 증가가 상피세포에서 먼저 이루어지는지 혹은 , 주위의 기질세포에서 먼저 일어나는지에 대해서도 아직 모른다. 그러므로 COX-2가 어떻게 대장암 세포 성장을 촉진시키는지에 대한 정확한 기전에 대한 이해가 아직 없는 실정이고, COX-2에 의해 생산된 여러 PG 가운데 어떤 PG가 어떤 기능을 가지고 대장암 세포의 성장을 촉진시키는지에 대한 연구도 현재 활발히 진행 중이다. 또 PG는 상피 세포에 직접 작용하는지 , 아니면 주위의 기저세포에 작용해서 그 기능을 나타내는지에 대한 연구도 밝혀야 할 연구 분야 중의 하나이다 . 임상적인 과제로는 대장 용종에서 선종 -대장암 순서로 진행되는 과정을 선택적 COX-2 억제제가 완전히 정지 시킬 수 있는지? 대장암의 화학적 예방을 위해 사용할 경우 선택적 COX-2 억제제의 장기 사용에 따른 부작용은 무엇인가? 그리고 장기 사용에 따른 비용 -효과면에서는 얼마나 효율성이 있는지 ? 진행성 대장암에서 완전히 제거 후에 재발방지를 위해 선택적 COX-2 억제제 사용이 가능한지? 등 아직 해결해야 할 질문이 많다.were isolated on 1.0% formaldehyde agarose gel for the detection of cPLA2, COX-2 and PGI2S mRNA expression. 28s RNA was used for loading control. This result showed coincidently and coordinately expressed mRNA of cPLA2, COX-2 and PGI2S. (B) Western analysis of cPLA2, COX-2, and PGI2S. RIE-iH-Ras cells were treated with 5 mM IPTG for the indicated times and lysed in lysis buffer. Fifty microgram of lysates in each wel were fractionated by SDS-polyacrylamide gel electrophoresis. After electropho-resis, the protein was transferred to nitrocellulose membrane. The filters were blotted with the indicated antibodies and developed by chemiluminescence system. This result showed coincidently and cordinately expressed protein of cPLA2, COX-2, and PGI2S with the induction of Ha-Ras by IPTG. IPTG; Isoprophyl-1-thio-β-D-galactopyranoside.58 대한대장항문학회지 제 19 권 제 1 호 2003


The possibility for cyclooxygenase (COX) inhibitors in colorectal cancer prevention and theraphy is evident from epidemiologic data (reduction of colorectal cancer in nonsteroidal anti-inflammatory drugs (NSAIDs) users), animal experiments (nude mouse xenograft tumor reduced by NSAIDs or reduction of colorectal cancer in APCmin mouse and azoxymethane treated rat by using NSAIDs), and molecular genetics. Among two variant COX, inducible COX-2 enzyme is more involved in tumorigenesis than constitutive COX-1 enzyme and molecular method have given us insight into the mechanism of colorectal cancer development by COX-2 such as, apoptosis, angiogenesis, invasiveness, and immune modulation. Based on that COX-2 is involved in tumor promotion during colorectal cancer progress, a large number of prevention and treatment trials of colorectal cancer have been started. And many trials to elucidate the function of prostaglandin produced by COX-2 are now in progress.


The possibility for cyclooxygenase (COX) inhibitors in colorectal cancer prevention and theraphy is evident from epidemiologic data (reduction of colorectal cancer in nonsteroidal anti-inflammatory drugs (NSAIDs) users), animal experiments (nude mouse xenograft tumor reduced by NSAIDs or reduction of colorectal cancer in APCmin mouse and azoxymethane treated rat by using NSAIDs), and molecular genetics. Among two variant COX, inducible COX-2 enzyme is more involved in tumorigenesis than constitutive COX-1 enzyme and molecular method have given us insight into the mechanism of colorectal cancer development by COX-2 such as, apoptosis, angiogenesis, invasiveness, and immune modulation. Based on that COX-2 is involved in tumor promotion during colorectal cancer progress, a large number of prevention and treatment trials of colorectal cancer have been started. And many trials to elucidate the function of prostaglandin produced by COX-2 are now in progress.