- 學位論文
原位口腔癌動物模式之建立與魚藤素抑制口腔癌轉移之探討
Establishment of orthotopic oral cancer models and evaluation of the inhibition effects of deguelin on tumor metastasis
摘要
根據2006年統計，口腔癌已成為台灣所有癌症死亡原因的第六名。而以男性癌症十大死亡原因來看，口腔癌則排名第五名。發病後除了會使患者的外表看起來很不健全之外，在最近的二十幾年內其五年小於50%的存活率並沒有明顯提升。鱗狀上皮細胞癌在口腔以及頜面區為最常發生的口腔癌，由於它的易轉移以及易入侵的能力而常導致較差的預後結果。在我們的研究中，我們首先決定不同的慢病毒劑量對七株口腔癌細胞株以及OMF的感染效率。藉由得到的感染效率結果，我們利用帶有綠色螢光蛋白以及冷光酶的慢病毒以20 MOI來感染Ca922以及SAS來建立能持續表現綠色螢光蛋白以及冷光酶的Ca922-GL和SAS-GL的細胞株。藉由這兩株細胞株，我們在小鼠建立起 Ca922以及SAS的原位腫瘤模式。在生物冷光影像觀察的結果中，我們發現Ca922是較不會轉移的細胞株，而SAS則是較會轉移的細胞株且腫瘤的生長速度也比較快。在SAS的原位腫瘤動物模式中，我們發現會轉移到唾腺的區域。然而，在Ca922的原位腫瘤動物模式中，則不會發現在此區域有轉移的腫瘤。 Deguelin是一種天然萃取的化合物，為一種AKT抑制劑。在細胞存活測試的實驗中，我們發現Ca922、Cal27以及SAS是對deguelin較敏感的口腔癌細胞株。之後，我們在腫瘤生長較快的SAS原位腫瘤模式以0.8 mg/kg和4 mg/kg 的deguelin劑量來餵食老鼠，觀察是否能抑制腫瘤的大小。在以4 mg/kg餵食的實驗組，其腫瘤大小相較於對照組有顯著的變小。而在劑量較低的0.8 mg/kg餵食的實驗組，其腫瘤大小也有明顯的抑制。由我們的研究結果顯示，deguelin可以有效的抑制口腔癌腫瘤大小的生長。未來在治療口腔鱗狀上皮細胞癌時，deguelin或許可被視為一種新的策略。
並列摘要
In Taiwan, oral cancer is the sixth leading cause of cancer-related death in year 2006, and it is the fifth leading cause of cancer-related deaths in male population on this island. The disease causes great morbidity, and the five-year survival rate of less than 50 % has not improved in more than two decades. Squamous cell carcinoma (SCC) is the most frequently a occurred cancer in the oral and maxillofacial regions, and its metastatic and invasive abilities tendencies made it difficult in prognostic control. In our study, we determined infection efficiencies in seven oral cancer cell lines and oral mucosa fibroblast (OMF) with different lentivirus dosage. The results suggested that using lentivirus for gene delivery is a promising method. We used 20 MOI GL-lentivirus to infect Ca922 and SAS cell lines to establish stable cell lines with GL expression. The Ca922-GL and SAS-GL orthotopic tumor models were established by these two stable cell lines. Based on bioluminescent imaging observation, SAS was highly invasive cell line, while Ca922-GL was not an invasive cell line in vivo. In SAS-GL orthotopic model, a metastatic tumor was observed on salivary gland. However, in Ca922-GL orthotopic model, no metastatic tumor was found in mice at all. Deguelin is a natural product and an AKT inhibitor. In cell viability assay, Ca922, Cal27, and SAS were sensitive to deguelin. To determine the inhibition efficacy of deguelin treatment on tumor growth, we used SAS-GL orthotopic tumor model with 0.8 mg/kg and 4 mg/kg deguelin treatment. In 4 mg/kg deguelin treatment, the tumor volume in SAS-GL orthotopic tumor model was significantly smaller than the control group. In addition, treatment with 0.8 mg/kg deguelin in SAS-GL orthotopic tumor model also resulted in a smaller tumor. Overall, our results indicated that the tumor growth of oral cancer could be inhibited by deguelin treatment, and this novel strategy may provide an additional treatment for OSCC
參考文獻
延伸閱讀
- 林群書（2019）。魚針草內酯治療頭頸部鱗狀細胞癌的分子機制研究〔博士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1401201907344700
- 林恆如（2012）。雜交條紋鱸抗菌胜肽Piscidin-1在人類纖維瘤細胞誘導細胞凋亡與細胞壞死 暨 以Cre-loxP技術調控魚類生殖生理之基礎研究與應用〔博士論文，國立臺北科技大學〕。華藝線上圖書館。https://doi.org/10.6841/NTUT.2012.00289
- 陳瀅（2009）。抗癌藥物造成人類甲狀腺濾泡癌細胞死亡之機制:PPARγ促效劑與蟲草素的作用探討〔博士論文，國立臺灣大學〕。華藝線上圖書館。https://doi.org/10.6342/NTU.2009.02817
- 蔡忠勳（2008）。細胞毒T淋巴抗體-4基因與血管加壓素轉化酶基因多型性於南台灣原住民口腔癌前病變相關性之探討〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://doi.org/10.6832/KMU.2008.00016
- 蔡閏旭（2011）。Validation of the integrins as tumor markers of oral squamous cell carcinoma〔碩士論文，高雄醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0011-1107201121381200