摘要
癌症為全球性之疾病，不分種族、年齡、性別皆有得到癌症的風險，尋找治療癌症之方法為目前世界流行之議題，其中以植物萃取物作為抗癌藥物的研究更是層出不窮。大麻植株有兩種主要的萃取成分，一種為具有精神活性的四氫大麻酚(THC)，另一種則為大麻二酚(CBD)，大麻二酚可以用來治療多種精神相關疾病，自大麻二酚被發現以來，經過多年研究發展發現其具有抑制發炎、抗氧化及抗癌作用。我們實驗室經過前期實驗結果發現，大麻二酚對於部分癌細胞株具有抑制生長的效果，因此我們對於大麻二酚的抑制癌症的功能產生濃厚的興趣。 在癌症的發展過程中上皮-間質細胞轉化(EMT)扮演著重要的角色，癌細胞透過EMT獲得間質細胞的特性，使癌細胞更利於遊走、移動，被認為與癌症轉移有密切的關聯。因此本論文目的在於探討大麻植株萃取物大麻二酚如何抑制癌細胞株之生長與其對於EMT機制的影響。我們發現大麻二酚降低癌細胞株生長速率，且會抑制癌細胞非貼附型生長。在細胞核的染色結果中，大麻二酚造成了細胞核呈現不完整、分裂成細小的囊泡且染色體壓縮的現象，在流式細胞儀的結果顯示正在誘發細胞產生程序性的死亡。另外我們觀察與細胞凋亡相關的蛋白質的表現，諸如P53和caspase家族以及BCL-2家族的蛋白質，證實確實與細胞凋亡相關。細胞發生EMT時蛋白質的表現會有所增減，我們的結果發現EMT的標誌蛋白Vimentin、Slug A7、α-sma、β-catenin顯示經過大麻二酚的處理，抑制細胞產生EMT。
並列摘要
Cancer is a global disease, regardless of race, age or gender, there is a risk of cancer. Finding a way to treat cancer is a popular topic in the world, and researches on using plant extracts as anticancer drugs are emerging one after another. There are two main extractive components of cannabis sativa plants. trans-Δ9 -tetrahydrocannabinol (THC) is considered the main psychoactive component in cannabis. And the other is cannabidiol (CBD), which can be used to treat a variety of psychological disorders. Since the discovery of CBD, it has been found that the anti-inflammatory, antioxidant and anti-cancer effects. Our previous data revealed that cannabidiol has an inhibitory effect on tumor cell growth. Therefore, we have a strong interest in the function of CBD in cancer. Epithelial-mesenchymal transition (EMT) plays an important role in the development of tumor. Cells undergoing EMT shows mesenchymal phenotype. It is considered to be highly related to metastasis and drug resistance. Recent study is to investigate how CBD inhibits tumor cell growth and its effect on the mechanism of EMT. We found that CBD reduces the growth rate and inhibits non-adherent growth of cancer cells. In addition, the nuclear stain showed that the nucleus divided into small vesicles and chromosomal condensation after CBD treatment. Moreover, the results suggest that CBD induced the programmed cell death by flow cytometry analysis. We further observed the expression of apoptosis-related proteins, such as P53, caspase family and BCL-2 family, confirming that it is related to apoptosis. Also, we examined the EMT marker, such as Vimentin, Slug A7, α-sma, β-catenin. Finally, results demonstrated that treatment of CBD inhibited the EMT progression.