人體細胞護衛因子5-MTP 可抗癌症2012/08/10 【聯合晚報╱記者李樹人╱台北報導】 治療癌症，不用化療、放療或標靶藥物，光靠人體抗癌基因也能抗癌！國家衛生研究院院長伍焜玉今天公布最新研究成果，研究團隊發現原本存在人類細胞內的抗癌護衛因子「5-MTP」，可對抗身體發炎，並抑制癌症轉移與生長。
老鼠注射5-MTP 肺癌腫瘤縮小一半 為了解「5-MTP」的抑癌效果，研究人員進行動物實驗，先將肺癌細胞打進老鼠體內，讓老鼠罹患肺癌，癌細胞轉移至其他部位，再每三天注射一次「5-MTP」，進行為期52天的實驗。結果發現，注射「5-MTP」50天後，肺癌腫瘤明顯縮小，只剩原本腫瘤的一半。原本轉移癌細胞也逐漸被殲滅，癌細胞數量減少，轉移部位腫瘤也縮小許多。這項研究成果備受國際專家學者肯定，已刊登於最新一期「美國國家科學院刊」。伍焜玉指出，為了加速研發腳步，已與國外製藥研究單位合作，進行人體試驗。這項研究歷經十多年，伍焜玉表示，2002年他發現人體內的纖維細胞會釋放抑制Cox-2（環氧化酵素）的一種小分子。Cox-2一旦過分表現，就會影響嚴重發炎，進而促使腫瘤生長、轉移。但受限於當時生化及檢驗技術，遲遲未能找出這個特殊小分子的化學結構。近年「分析代謝體儀器」（LC-MS ）更為敏感，極微量的小分子化合物也可被偵測到。歷經兩年多的篩選尋找，終於找到細胞護衛因子的真正化學結構「5-MTP」。伍焜玉表示，環境中的致癌物質越來越多，但罹癌人數未大增。顯示每個人體內本身就有具備抗癌基因。伍焜玉強調，細胞護衛因子「5-MTP」是人類消炎抗癌的重要內在保護因子。未來一旦進入臨床治療，就能協助癌症患者抗癌，讓腫瘤變小。
Cyclooxygenase-2 (COX-2) expression is induced by mitogenic and proinflammatory factors. Its overexpression plays a causal role in inflammation and tumorigenesis. COX-2 expression is tightly regulated, but the mechanisms are largely unclear. Here we show the control of COX-2 expression by an endogenous tryptophan metabolite, 5-methoxytryptophan (5-MTP). By using comparative metabolomic analysis and enzyme-immunoassay, our results reveal that normal fibroblasts produce and release 5-MTP into the extracellular milieu whereas A549 and other cancer cells were defective in 5-MTP production. 5-MTP was synthesized from L-tryptophan via tryptophan hydroxylase-1 and hydroxyindole O-methyltransferase. 5-MTP blocked cancer cell COX-2 overexpression and suppressed A549 migration and invasion. Furthermore, i.p. infusion of 5-MTP reduced tumor growth and cancer metastasis in a murine xenograft tumor model. We conclude that 5-MTP synthesis represents a mechanism for endogenous control of COX-2 overexpression and is a valuable lead for new anti-cancer and anti-inflammatory drug development.
Published online before print July 31, 2012, doi: 10.1073/pnas.1209919109
PNAS July 31, 2012
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