Medical Faculty News v25i1

癌細胞需要養分，而我們正在找出肝癌 細胞在新陳代謝上的需求和潛在的分子途徑， 最終是希望找到標靶治療的方向。 Liver Cancer and The Dark Side of Antioxidants Antioxidants have been popularly embraced as a way to combat the free radicals that can harm human cells. But research by Dr Carmen Wong Chak-lui , Assistant Professor in the Department of Pathology, has shown they have the opposite effect in liver cancer cells: they can help these cells to survive and grow. The finding was a key discovery in her research on the metabolism and microenvironment of liver cancer. Dr Wong and her team showed that while oxidative stress can kill liver cancer cells, these cells have developed a way to survive this attack by producing antioxidants through the pentose phosphate pathway, folate cycle, malate metabolism, and serine synthesis pathway. As more antioxidants are produced, the cancer cells can grow. The finding applies not only to liver cancer but other cancers that have the same metabolic pathway, such as colorectal and lung cancers. But the team also identified a possible way to counter this effect by targeting enzymes such as transketolase, methylenetetrahydrofolate dehydrogenase, malate enzyme, and phosphoglycerate dehydrogenase to create metabolic vulnerabilities in the cancer cells that enhance their sensitivity to existing drug treatment. Overall, the findings suggest that dietary antioxidant supplements should be used with caution. Dr Wong currently is involved in a genome-wide screening study to investigate the mechanisms that allow liver cancer to survive therapies and metabolic stress, and the role of liver cancer metabolites on different immune cells. “Cancer cells need nutrients and we are trying to identify the metabolic requirements and underlying molecular pathways of liver cancer, which we hope will lead to targets for therapy,” she said. 肝癌與抗氧化劑不為人知的一面 現時普遍認為，自由基對人體細胞有害，而抗 氧 化劑則 經常被視為可以有效對抗自由基；但是根據病理學系助理教 授 黃澤蕾博士 的發現，抗 氧 化物在肝癌細胞裡，並不能發生預 期的作用，更甚的是抗 氧 化劑有助癌細胞存活及繁殖。這是她 致力於研究肝癌細胞新陳代謝及其微環境的重要成果。 黃博士及她的研究團隊發現，雖然 氧 化逆境可以殺死 肝癌細胞，但是這些癌細胞卻反而能 夠 通過磷酸戊糖途徑、 葉酸循環、蘋果酸新陳代謝，和絲 氨 酸合成途徑製造抗 氧 化 物，逃避攻擊而存活下來。當癌細胞製造更多抗 氧 化物時， 本身便可以持續生長。這項研究成果不單在肝癌細胞的研究 上能 夠 成立，也同時可以應用在其他有相同代謝途徑的癌症 上，例如結直腸癌和肺癌。 不過，研究團隊同時亦找出一個方法抗衡上述情況， 針對轉 酮 醇 酶 、亞甲四 氫 葉酸脫 氫酶 、蘋果酸縮合 酶 、磷酸 甘油脫 氫酶 等酵素，在癌細胞裡製造代謝性的漏洞，讓癌細 胞更易遭受攻擊，從而加強藥物對癌細胞治療的有效性。總 括而言，是項研究成果建議使用口服抗 氧 化補充品的時候， 宜小心謹慎。 黃博士現正進行一項全基因組學篩 查 研究，希望找出 容許肝癌細胞在治療期間和代謝逆境中依然存活的機制，以 及在不同免疫細胞中的肝癌代謝物的作用。 黃博士說：「癌細胞需要養分，而我們正在找出肝癌 細胞在新陳代謝上的需求和潛在的分子途徑，最終是希望找 到標靶治療的方向 。」 42 Feature