環(huán)氧化酶(cyclooxygenase,COX)是參與花生四烯酸的環(huán)氧酶代謝途徑中的限速酶，可催化花生四烯酸轉(zhuǎn)化為前列腺素(prostaglandins,，PGs)。近年來(lái)研究顯示,，COX-2在一些腫瘤中存在過(guò)度表達(dá)現(xiàn)象,，提示COX-2可能與腫瘤的發(fā)生發(fā)展密切相關(guān)。
環(huán)氧合酶（COX）-2在肺癌中起著重要作用,，是肺癌侵襲和轉(zhuǎn)移的關(guān)鍵因素,。傳統(tǒng)中藥川芎有效成分川芎嗪（TMP），歷來(lái)用于治療神經(jīng),、血管和心血管疾病,。最近Int J Oncol雜志刊登論文報(bào)道TMP對(duì)癌癥病人有有利的影響。然而,，一直以來(lái)TMP對(duì)肺癌的功能和機(jī)制尚未被闡明,。
在這項(xiàng)研究中，研究人員探究了在體外和體內(nèi),，TMP的分子靶點(diǎn)是否是COX-2,。結(jié)果表明，川芎嗪抑制A549細(xì)胞增殖和細(xì)胞周期進(jìn)程,，并且具有劑量和時(shí)間依賴性,。在體外川芎嗪處理A549細(xì)胞能顯著抑制COX-2和MMP-2/TIMP-2的活性，降低腫瘤細(xì)胞侵襲能力,。
此外,，體內(nèi)實(shí)驗(yàn)顯示川芎嗪明顯抑制A549轉(zhuǎn)移裸鼠模型的腫瘤的生長(zhǎng)，其與降低COX-2的表達(dá)有關(guān),。這項(xiàng)臨床前研究證實(shí)COX-2通路抑制劑對(duì)人肺腺癌細(xì)胞株A549的治療非常有效,，TMP可能成為一種新的抗腫瘤藥物，川芎嗪能起到化學(xué)預(yù)防和治療非小細(xì)胞肺癌,。（生物谷：Bioon.com）
doi:10.3892/ijo.2012.1375
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Inhibition of cyclooxygenase-2 by tetramethylpyrazine and its effects on A549 cell invasion and metastasis
Chun-Yan Zheng, Wei Xiao, Mao-Xiang Zhu, Xiu-Jie Pan, Zhi-Hua Yang, Sheng-Yu Zhou
Cyclooxygenase (COX)-2 plays an important role in tumorigenesis and has been implicated to be a critical factor for invasion and metastasis of lung cancer. Tetramethylpyrazine (TMP), an effective component of the traditional Chinese medicine Chuanxiong, has been traditionally used in treating neurovascular and cardiovascular diseases. Recently TMP has been reported to have beneficial effect in cancer patients. However, the function and the mechanism of TMP in lung cancer have not been elucidated to date. In this study, we investigated the in vitro and in vivo effect of TMP in tumorigenesis and whether COX-2 is a molecular target of TMP. We showed that TMP exhibited a dose- and time-dependent inhibition on A549 cell proliferation by suppressing cell cycle progression. In vitro treatment of A549 cells with TMP resulted in a significant inhibition of invasion, associated with reduced activities of COX-2 and MMP-2/TIMP-2. Furthermore, in vivo experiments showed that TMP significantly suppressed metastatic growth of A549 cells and COX-2 expression in metastatic nude mouse model. This preclinical study provides the first evidence for the novel anti-tumor effects of TMP as a COX-2 pathway inhibitor in human adenocarcinoma cell line A549. These studies suggest that TMP may serve as an effective agent for the treatment and chemoprevention of non-small cell lung cancer.
