封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 39 陳修平教授從事藥理學研究近20年，發表SCI期刊論文150餘篇，申請專利6項。曾主持多個國家和澳門的科研項目，亦曾 獲兩屆澳門科學技術獎自然科學獎。 Prof Chen Xiuping has studied pharmacology for nearly two decades. He has published more than 150 papers in SCI-indexed journals, and has applied for six patents. He has headed scientific research projects in mainland China and Macao. He is a two-time recipient of the Macao Science and Technology Award in the ‘Natural Science Award’ category. 陳修平 教授發現 中藥虎杖 具有誘導 程序性 壞死的 成分 Prof Chen Xiuping has identified several ingredients in Reynoutria japonica that can induce necroptosis 死亡，如人之意外死亡。程序性壞死是 一種非凋亡的程序性死亡方式。細胞 發生這種死亡時會啟動RIP1、RIP3和 MLKL蛋白，MLKL蛋白在細胞膜上形 成小孔，導致細胞內外滲透壓改變，導 致細胞死亡。他進一步比喻道：「這時 細胞發生腫脹，嚴重時就像氣球般脹起 來，最終脹破死亡。同凋亡一樣，程序 性壞死也可直接殺傷癌細胞。」 為甚麼要研究中藥誘導程序性壞死呢？ 陳教授表示，多年來中藥抗癌基礎研究 集中於誘導凋亡。但與臨床應用的西藥 相比，中藥誘導凋亡的藥效比較低。尤 其是，癌細胞很「狡猾」，多次用藥後 就耐藥了，亦即凋亡對它無可奈何了。 這時候誘導程序性壞死，就可以殺傷這 些凋亡耐受的癌細胞。因此，為了凸顯 中藥的特色和優勢，課題組集中尋找和 鑒定能誘導程序性壞死的中藥成分。 「經數年研究，發現來自虎杖、丹參 等中藥具有數個這樣的成分。」 陳教授指出，雖然尚處於基礎研究階 段，藉程序性壞死抗癌的策略已於動物 模型上證實。鑒於臨床抗腫瘤藥物凋亡 耐受現象日益常見以及中藥誘導凋亡的 低藥效，「這或將是未來中藥抗癌的一 個頗具潛力和前瞻性的研究方向。」 death of cells in an extreme environment, which is similar to the accidental death of a person. Necroptosis is a non-apoptotic method of programmed death. When this form of cell death occurs, it activates RIP1, RIP3, and MLKL proteins. MLKL proteins form small pores in the cell membrane, resulting in changes in osmotic pressure inside and outside the cell, which in turn causes cell death. He explains: ‘The cells “swell” like balloons, and when the swelling reaches a certain point, the cells burst and die. Like apoptosis, necroptosis can also directly kill cancer cells.’ When asked why he decided to study necroptosis induced by Chinese medicine, Prof Chen says that for years, basic research on traditional Chinese medicine in cancer treatment has focused on the induction of apoptosis. However, compared with clinically applied Western medicine, the efficacy of Chinese medicine in inducing apoptosis is relatively low. One of the reasons for this outcome is that cancer cells are ‘cunning’ - they become resistant to drugs over time, and when that happens, apoptosis is not effective any more. This is where necroptosis comes in. Necroptosis can kill cancer cells that are resistant to apoptosis. Therefore, Prof Chen and his team are studying the characteristics and advantages of Chinese medicines, in an effort to find Chinese medicine ingredients that can induce necroptosis. ‘After several years of hard work, we have identified several ingredients in traditional Chinese medicine such as Reynoutria japonica and Salvia miltiorrhiza that can induce necroptosis,’ says Prof Chen. Although the team is still at the basic research stage, Prof Chen says that the efficacy of this strategy of inducing necroptosis of cancer cells has already been confirmed in animal testing. He says, ‘In view of the increasingly common resistance to cancer drugs and the low efficacy of Chinese medicine‑induced apoptosis, this may be a promising research direction for treating cancer with traditional Chinese medicine.’
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