透過您的圖書館登入
IP:34.200.248.66
  • 學位論文

研究在不同生長環境下結腸癌細胞對抗癌藥物之敏感性

Study of the anticancer drug sensitivity of colon cancer cell in the different growing environments

指導教授 : 曾淑玲
若您是本文的作者,可授權文章由華藝線上圖書館中協助推廣。

摘要


在英美,癌症為十大死亡原因之第二位,僅次於心臟血管疾病;在台灣,國人十大死因第一名為惡性腫瘤,其中大腸直腸癌(Colorectal cancer)是常見的惡性腫瘤之一。大腸直腸癌發生率在男性當中高居第一,女性則僅次於乳癌,加上近年來發病率及死亡率有逐漸上升的趨勢,因此對於大腸直腸癌的預防與治療需更加重視。在過去數十年中,雖然在手術、放射治療及基礎研究中做過多種努力,但其五年之存活率,卻仍然沒有多大的改進,加上已經有許多文獻指出,大腸直腸癌的發生率和環境、飲食習慣等有密切的關聯,因此若無法有效預防大腸直腸癌,就需要先提升其存活率和治癒率,找尋一個更有效率治療大腸直腸癌的方式,這也成為當今社會一個重要的課題。從現有的抗癌藥物加上改變癌細胞生長環境方面著手,希望能提升癌細胞對抗癌藥物的敏感度,以至於提升大腸直腸癌的治癒率。 已有文獻指出,高濃度葡萄糖確實會促進癌細胞的增生,也會使抗癌藥物的敏感度下降,但在大腸直腸癌細胞內卻沒有詳細的機轉探討。因此,欲了解大腸癌細胞株SW480、SW620在不同濃度之葡萄糖環境下,對藥物的敏感性是否有影響,所以利用目前治療大腸直腸癌主要用藥5-FU(Fluorouracil)進行加藥處理,觀察細胞存活率,MTT assay(3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)結果顯示,生長於低濃度葡萄糖的大腸癌細胞具有較高的藥物敏感度。接下來使用流式細胞儀觀察大腸直腸癌細胞株在不同葡萄糖濃度的環境下,其細胞週期過程是否有不同,結果發現經藥物刺激下,高濃度葡萄糖的S期增加比率較低葡葡糖多。另一方面有許多文獻指出,癌幹細胞對藥物耐受性有很大的影響,因此欲了解不同濃度之葡萄糖是否會增加癌幹細胞的活性,所以使用懸浮培養(sphere culture)的方式觀察球狀細胞的數量及直徑大小,結果發現高濃度葡萄糖有助於癌幹細胞之生成及活性。 綜合以上研究結果將可以得知,不同濃度的葡萄糖對大腸直腸癌細胞藥物耐受性及癌幹細胞有一定的影響力,這將提供病患血糖濃度的控制對大腸直腸癌治療策略的影響,讓大腸直腸癌患者的治癒能力和效率有更大的提升。

並列摘要


In the UK and the USA, cancer is the second cause of death for the top ten, second only to cardiovascular disease. In Taiwan, one of the top ten causes of death is malignancy, in which colorectal cancer is one of the common malignancies. The incidence of colorectal cancer ranks first among men, women are second only to breast cancer. In recent years, morbidity and mortality have gradually increased, so for colorectal cancer prevention and treatment needs more attention. In the past few decades, although many efforts done in surgery, radiation therapy and basic research, but its five-year survival rate still not much improvement, and there have been many literature suggests that environment, eating habits are closely related to the incidence of colorectal cancer, therefore, if it can't effectively prevent colorectal cancer, need to first increase its survival rate and cure rate, to find a more efficient treatment of colorectal cancer, which has become an important issue in today's society. From the existing anti-cancer drugs combined with changes in cancer cell growth environment aspects, hoping to enhance the anticancer drugs sensitivity of cancer cells that enhance the cure rate of colorectal cancer. Existing literature that high glucose promotes cancer cells proliferation, and make anti-cancer drug sensitivity decreased, but in colorectal cancer cells don't have a detailed mechanism to explore. Therefore, to understand the colorectal cancer cell lines SW480, SW620 in different concentrations of glucose environment, whether impact to the drug sensitivity, So use the 5-FU (Fluorouracil) that is the current mainly treatment of colorectal cancer, dosing treatment to observe the cell survival rate, MTT assay results show colorectal cancer cells grown at low concentrations of glucose have higher drug sensitivity. Next, using the flow cytometry to observe the expression of colorectal cancer cells in different glucose concentration environment, whether the cell cycle process is different. The results showed that under the stimulation of drugs, high glucose increase the S phase. On the other hand, there are many literatures that cancer stem cells have a significant effect on the drug resistance. Therefore, to understand whether different concentrations of glucose will increase the activity of cancer stem cells, so use sphere culture to observe the number of spherical cells and diameter size, the results showed that high concentrations of glucose contributes to cancer stem cell growth and activity. Based on the above results will be known, different concentrations of glucose have a certain influence on colorectal cancer cell drug resistance and cancer stem cells, control glucose concentration that will provide a effect on the treatment strategy for colorectal cancer patients, let healing ability and effectiveness have more improvement for colorectal cancer patients.

參考文獻


許蕙子 ; 宋明達 ; 李直隽 ; 張玉芳 ; 戚謹文(2011)。The Role of Gut-Enriched Krüppel-Like Factor (GKLF)/KLF4 in Gastrointestinal Tract-Related Cancers。臺灣癌症醫學雜誌 27:5 2011.10[民100.10] 頁191-199.
Birsoy, K., Possemato, R., Lorbeer, F. K., Bayraktar, E. C., Thiru, P., Yucel, B., . . . Sabatini, D. M. (2014). Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides. Nature, 508(7494),108-112.
Campisi J, Gray HE, Pardee AB, Dean M, Sonenshein GE (1984). "Cell- cycle control of c-myc but not c-ras expression is lost following chemical transformation". Cell. 36 (2): 241–247.
Cb Penny, B. L. M. (2015). Cd133/Epcam Cancer Stem Cell Markers of Tumour Stage in Colorectal Cancer Cells. Journal of Tissue Science & Engineering, 06(01).
Chen H, Luo Z, Dong L, Tan Y, Yang J, Feng G, Wu M, Li Z, Wang H. CD133/prominin-1-mediated autophagy and glucose uptake beneficial for hepatoma cell survival. PLoS One. 2013;8(2):e56878.

延伸閱讀