封面專題•COVER STORY 澳大新語•2020 UMAGAZINE 22 33 李子安教授主要研究G蛋白偶聯受體（GPCR）信號對女性生殖系統功能及GPCR對卵巢癌的發 展及擴散中的作用，已發表SCI期刊論文45篇。 Prof Leo Lee Tsz On focuses on the role of GPCR signalling in the female reproductive system, as well as its impact on the development and spread of ovarian cancer. He has published 45 papers in SCI-indexed journals. 血管緊張素II及其受體對增強卵巢癌多細胞球囊形成、生長和轉移的分子機制 The molecular mechanism by which angiotensin II and its receptors enhances the formation, growth, and metastasis of multicellular spheroids of ovarian cancer 卵巢癌的擴散方式之一，是癌細胞從卵 巢脫落，形成具抗藥性的球狀體並擴散 到其它器官。李教授指出，這些球狀體 的形成與血管緊張素II大有關係。在正常 情況下，血管緊張素II會在血管內調控血 壓，較少在卵巢出現，但李教授發現卵 巢癌細胞會自行產生這種激素。他說： 「通過固醇調節元件結合蛋白途徑，血 管緊張素II的受體會促進不飽和脂肪酸 的含量來減少細胞壞死，令癌細胞更容 易轉移。」 有見及此，李教授的團隊合成了一種小 分子干擾核糖核酸（siRNA），用來抑 制血管緊張素II的受體運作，減少卵巢 癌擴散。但這種siRNA容易在體內被分 解，而且無法穿透細胞膜進入癌細胞。 他的團隊於是研究運用納米材料「樹枝 狀聚合物」將siRNA包住，協助進入卵 巢癌細胞，阻止血管緊張素II受體的運 作。他指這項研究已經進入動物測試階 段，有望使卵巢癌治療效果更為顯著。 Some ovarian cancer cells detach from the ovary. After that, they reproduce and form drug-resistant multicellular spheroids, which then spread and implant to other organs. According to Prof Lee, the formation of these spheroids is closely related to angiotensin II. This hormone normally regulates blood pressure in the blood vessels and is not commonly observed in the ovary. However, he found that ovarian cancer cells are able to produce angiotensin II. ‘Through the sterol regulatory element-binding protein pathway, receptors of angiotensin II increase the production of unsaturated fatty acids, which help reduce cellular necrosis and promote cancer cells’ metastasis,’ says Prof Lee. In light of this discovery, his team created a type of small interfering RNA (siRNA) to block the operation of the receptors of angiotensin II, in order to reduce ovarian cancer cells. However, this siRNA, likely to be broken down in blood, cannot penetrate the membranes of cancer cells. Prof Lee’s team is working to develop a technique to wrap siRNA with a type of nanomaterial known as ‘dendrimer’. This material could help to deliver the siRNA to the tumour and enables the siRNA to enter the ovarian cancer cell and to suppress the receptors of angiotensin II. Meanwhile, his team has started animal testing, which is an important step towards more effective ovarian cancer treatment.
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