利用小鼠結腸癌類幹細胞之動物模式及評估其特性並探討魚油合併硒酵母營養介入之影響

外文標題: 
Using a mouse model to assess colon cancer stem-like cell performance and examine eliminate capacity following dietary supplementation with fish oil and selenium yeast
校院系所: 
國立臺灣海洋大學食品科學系
指導教授: 
吳彰哲
出版年份: 
2014年
主題類別: 
摘要: 

目前以傳統方式治療癌症可以殺死大部分癌細胞,然而惡性程度高的癌細胞卻可以繼續存活,最近研究指出這群惡性程度高的癌細胞為癌症幹細胞 (Cancer stem cells, CSCs),CSCs具有抗藥及轉移之特性,是腫瘤惡化及治療後復發重要因素。結腸直腸癌 (Colorectal cancer, CRC) 是常見惡性腫瘤之一,早期不易發現,容易轉移至肝臟、肺臟。已有報導指出,從ω3多元不飽和脂肪酸衍生之魚油可抑制腫瘤生長及轉移;硒酵母亦具有抑制腫瘤細胞的侵襲和血管生成之能力,然而,魚油與硒酵母合併作用是否具有減緩癌症幹細胞的不良影響仍不明確。首先我們測試BALB/c小鼠結腸癌細胞 (CT26) 是否具有癌症幹細胞之特性,實驗利用添加化療藥物順鉑 (cisplatin) 進行培養篩選存活細胞,結果顯示經順鉑培養之細胞具有較高抗藥性,且癌症幹細胞相關基因表現上升。因此,實驗後續利用CT26建立結腸癌類幹細胞研究模式,以Hoechst染劑篩選出的邊群細胞 (Side population cell, SP cell),其抗藥特性能力強,且癌症幹細胞相關基因表現高,與非邊群細胞相比亦具有較高細胞遷移及形成細胞群落能力。我們進一步證明SP 細胞的致腫瘤能力較強,會使小鼠體重流失嚴重及產生肺部轉移,且肺部中與轉移相關的趨化因子和基質金屬蛋白酶表現上升。此外,實驗更進一步利用魚油與硒酵母添加於飲食中,結果發現可以減緩小鼠體重流失及肺臟腫瘤轉移,且趨化因子與基質金屬蛋白酶表現被抑制。因此,魚油與硒酵母營養品補充可減緩由癌症幹細胞誘導癌細胞轉移之可能性。

外文摘要: 

Traditional cancer therapies are high efficiency to kill cancer cells, but some of the advanced malignancy cells can still survive. Recent studies have shown that the small population of tumor cells, known as cancer stem cells (CSCs). These CSCs have the ability to promote tumor drug-resistant and metastasis, and play an important role of malignant progression and recurrence. Colorectal cancer (CRC) is one of the common malignant neoplasm, that is difficult to discover in the early stage and often metastasizes to liver and lung. Omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil has been reported has the capability to inhibit tumor growth and metastasis. Selenium yeast is also able to suppress tumor invasion and anti-angiogenesis. However, whether the combination effects of fish oil and selenium yeast mitigate the adverse effects of CSCs is still unclear. First, we treat cells with chemotherapy drug (cisplatin) to characterize the drug resistant of CSCs in BALB/c mouse colon carcinoma cells (CT26). The results showed that the survival cells have higher chemo-resistance and CSCs-related gene expression. Therefore, we establish CT26 as a colon CSCs research model in the following experiments. We screen the side population cells (SP cells) in CT26 with Hoechst dye, which have better drug- resistance and higher CSCs-related gene expression. Furthermore, the migratory capacity and colony formation ability of SP cells are higher than non-population cells (NSP cells). In vivo, we demonstrate that SP cells have stronger tumorigenic ability, more body weight loss and lung metastasis. After analyses lung tissues, the gene expression of metastasis–associated chemokines and matrix metalloproteinases are increased. In further experiments, the dietary supplementation with fish oil and selenium yeast can attenuate body weight loss and lung metastasis. The expression of metastasis–associated chemokines and matrix metalloproteinases are suppressed. Thus, fish oil and selenium yeast supplementation can lower the possibility of cancer metastasis which caused by cancer stem cells.