消除人類癌腫瘤幹細胞的藥物

Abstract

第一部分: 利用鴉膽子水溶液萃取物清除突變上皮細胞生長因子接受體人類肺癌細胞 中文摘要 從古以來，傳統草藥已經被大部分的中國人作為常用藥物，也是東方國家廣泛接受的藥物。非小細胞肺癌是最常見的肺癌類型，早期很難被診斷出。突變的表皮生長因子受體已經成為新型抗癌治療的分子標靶。本論文所使用鴉膽子水溶液萃取物有效地減弱了在非小細胞肺癌具有突變EGFR L858R/T790M的生長。癌幹細胞具有抗藥性，轉移和癌症復發，並且可以影響腫瘤治療的發展。重要的是，抗藥性使腫瘤更惡化。本論文也探討了鴉膽子水溶液萃取物對非小細胞肺癌的癌幹細胞的療效與反應機制。鴉膽子水溶液提取物是具可以成為非小細胞肺癌放射性治療有潛力的藥物。

第二部分: 發展teroxirone成為有效治療肝癌細胞的藥物 中文摘要 Teroxirone (1,3,5-tris((oxiran-2-yl)methyl)-1,3,5-triazinane-2,4,6-trione)是三環氧化物抗腫瘤劑，此研究目的是確定teroxirone如何調控與凋亡相關的細胞死亡。 利用MTT檢測三種肝細胞癌細胞系：Huh7（突變體p53），HepG2（野生型p53）和Hep3B（p53-缺失型） assay(細胞存活檢測) 細胞存活率，利用流式細胞儀及西方點墨法觀察凋亡所導致的細胞死亡。本研究發現在Huh7 細胞所引起凋亡的細胞死亡是透過外在途徑。Teroxirone 可以誘導從Huh7腫瘤球體所純化出來的腫瘤幹細胞的凋亡並抑制Huh7腫瘤球體幹細胞特性。Part-I. The alleviated tumorigenicity of human lung cancer cells carrying mutated epidermal growth factor receptor by aqueousextract of Brucea javanica Abstract The traditional herbal medicine has been used as convenient medicine by the majority of the Chinese population the since recorded history and is still a widely accepted medicine in oriental countries. NSCLC (non-small cell lung cancer) is the most prevalent type of lung cancers which is hard to be diagnosed early. The mutated EGFR (epidermal growth factor receptor) has become a target in the development of novel anti-cancer therapeutic approaches. In this study, the aqueous BJ (Brucea javanica) extract has found effectively attenuated the growth of human NSCLC with mutant EGFR L858R/T790M. CSCs (cancer stem cells) are involved in drug resistance, metastasis and relapse of cancers and can influence the tumor therapy development. Importantly, drug resistance makes tumors more malignant. The work investigated the underlying mechanisms of aqueous BJ extract against CSCs of NSCLC. The study showed potential implication of aqueous BJ extract as new target therapy to human lung cancer.

Part-II. The development of teroxirone as an effective therapeutic agent against human hepatocellular carcinoma cells Abstract Teroxirone is an experimental triepoxide antitumor agent. The purpose of this study is to determine how teroxirone regulates growth of liver cancer cell. Three hepatocellular carcinoma cell lines, Huh7 (mutant p53), HepG2 (wild-type p53) and Hep3B (p53-null) cells, were used for experiments. The study included MTT assay for assessing cell viability, flow cytometry for evaluating apoptotic cell death and Western blot analysis for determining signal pathway activation. The findings suggested that teroxirone induced apoptotic cell death in p53-mutated Huh7 by stimulating extrinsic pathway that was reverted by caspase-3 inhibitor. Teroxirone also induced apoptosis and suppresses the stemness properties of the enriched Huh7 spheroids. The study implied that the small molecular weight molecule teroxirone is a potentially valuable agent to treat human hepatocellular carcinoma.