Dr Carmen Wong Chak-lui — Liver Cancer and The Dark Side of Antioxidants | 黃澤蕾博士 — 肝癌與抗氧化劑不為人知的一面

(中文版見於下方)

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.

Biography

Dr Carmen Wong Chak-lui graduated from The University of British Columbia (Canada) with a degree of Bachelor of Science in Microbiology and Immunology. She further completed her studies of Master of Science
in Biotechnology at HKUST and Doctoral degree in Cancer Biology at HKU, where she developed strong interests and passion in cancer research. In 2009, Dr Wong was awarded the Croucher Foundation Fellowship to receive her post-doctoral training under the Nobel laureate Professor Gregg Semenza at
The Johns Hopkins University (USA).

Dr Wong is currently Assistant Professor of the Department of Pathology, HKUMed and Principal Investigator of the State Key Laboratory of Liver Research, HKU. Her main research interest focuses on tumour
microenvironment formation, cancer metabolism and roles of hypoxia in cancer development. In 2017, Dr. Wong received the Croucher Innovation Award and HKU Outstanding Young Researcher Award. Dr Wong is also an elected member of The Hong Kong Young Academy of Sciences.

(This article was originally published in Medical Faculty News)

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 。」

簡歷

黃澤蕾博士於加拿大英屬哥倫比亞大學獲得微生物及免疫學學士學位之後，回港在香港科技大學取得生物科技碩士學位，再於港大醫學院獲取癌症生物學博士學位。2009年，她獲頒裘槎基金會裘槎博士後研究獎學金，隨即前往美國約翰·霍普金斯大學，在諾貝爾獎得主Professor GreggSemenza指導下從事博士後研究。

黃博士現時是港大醫學院病理學系助理教授，也是港大肝病研究國家重點實驗室首席研究員。她的主要研究範疇是腫瘤微環境的形成、癌細胞的新陳代謝，以及缺氧對發展中癌症的影響。2017年，她獲頒裘槎基金會裘槎前瞻科研大獎及香港大學傑出青年研究學者獎。黃博士亦獲選為香港青年科學院會員。

(原文刊登於港大醫學院 Medical Faculty News)