環氧合酵素 (cyclooxygenase；COX) 是將花生四烯酸 (arachidonic acid) 代謝成前列腺素 (prostagladin) 的速率限制酵素(rate-limiting enzyme)。目前人體內主要有兩種COX被發現，COX-1和COX-2。COX-1在細胞中會持續性穩定的表現；COX-2則是會被發炎因子、生長因子和細胞激素等刺激誘導產生，COX-2被認為有促進癌細胞生長的能力。噻唑烷二酮類藥物( thiazolidinediones; TZDs)，脂肪細胞分化轉錄因子的核接受器(peroxisome proliferator-activated receptor-γ; PPAR-γ)的配位體，在許多癌症的研究當中被指出具有抑制細胞生長、誘導細胞分化和細胞凋亡的能力。本篇研究目的在於要了解在A549細胞中使用TZD類藥物Tro (troglitazone) 對COX-2的調控路徑，以及此調控與細胞生存的影響。
研究結果顯示，Tro能經由活化MEK/ERK的路徑誘導COX-2。當對A549細胞預先處理PD98059 (MEK1抑制劑)，可以抑制由Tro所誘導的COX-2約48 %表現；以GW9662 (PPAR-γ抑制劑) 探求PPAR-γ 是否有參與在Tro對COX-2的調控中，結果發現在PPAR-γ被抑制的狀態下，Tro可以誘導多約53 %的COX-2表現。另外，由於Tro對A549細胞的生存率有time-depededent和dose-depedent的負向調控能力；加入NS-398 (COX-2抑制劑)可抑制部分Tro所誘導的COX-2表現，並且造成多於Tro單獨處理下的cytochrome c釋放，藉此可初步推論在A549細胞中，Tro誘導COX-2表現對於細胞生存是屬於正向的調控。根據以上結果得知，在A549細胞中Tro可藉由MEK/ERK和PPAR-γ這兩條不同路徑分別調控COX-2的表現。

Cyclooxygenases (COX) catalyze the rate-limiting steps in the conversion of arachidonic acid into prostaglandins and thromboxanes. There are two isoforms of COX, COX-1 and COX-2. While COX-1 is constitutively expressed in many tissues, COX-2 is normally not present in tissues and highly inducible by various stimuli such as inflammatory factors, growth factors and cytokine. COX-2 plays an important role in tumorigenesis. Thiazolidinediones are selective ligands for peroxisome proliferator-activated receptor-γ (PPAR-γ). They are capable of inhibiting cell proliferation, inducing cell differentiation and apoptosis in many tumor cells. This study aims to investigate the relationship of troglitazone ( Tro; a kind of TZD drug ) on COX-2 expression, control pathway, and cell viability in A549 human lung carcinoma cells.
In this study, Tro was shown to induce COX-2 expression through MEK/ERK pathway. PD98059, a selective inhibitor of MEK (upstream kinase of ERK), was found to black about 48 % of COX-2 expression induced by Tro. Pretreatment of cells with GW9662, a PPAR-γ antagonist, was shown to enhance 53 % COX-2 expression compared with Tro treated alone. Tro was found to reduce cell viability in time-and dose-dependent manners. To investigate the relationship between Tro-induced COX-2 expression and cell viability. NS-398, an COX-2 selective inhibitor, co-treatment with Tro was found to reduce Tro-induced COX-2 expression and induce more cytochrome c release compared with Tro-treated alone. Tro-induced COX-2 expression in A549 cells is seen to be a positive regulation for cell proliferation. These data suggest that COX-2 expression modulated by Tro through different MEK/ERK-dependent and PPAR-γ-dependent mechanism respectively.

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