Establishment of a Mouse Model to Assess Colon Cancer Stem-Like Cell Performance and Examine Eliminate Capacity Following Dietary Supplementation with Fish Oil and Selenium Yeast

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Project title

Code/計畫編號

MOST105-2320-B019-005-MY3

Translated Name/計畫中文名

建立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

Project Coordinator/計畫主持人

Chang-Jer Wu

Funding Organization/主管機關

National Science and Technology Council

Department/Unit

Department of Food Science

Website

https://www.grb.gov.tw/search/planDetail?id=12375895

Year

2018

Start date/計畫起

01-08-2018

Expected Completion/計畫迄

01-07-2019

Bugetid/研究經費

1000千元

ResearchField/研究領域

食品科技(工)

"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。結腸癌 (Colon cancer) 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。首先將在第一年計畫中建立BALB/c 小鼠結腸癌細胞(CT26) 的癌症類幹細胞之研究模式，分選具癌症幹細胞特性之邊群細胞(side population cell, SP)，鑑定其癌症類幹細胞相關特性，並探討其癌症幹細胞標誌、腫瘤趨化因子、發炎細胞因子、基質金屬蛋白酶基因表現、上皮間質轉化作用及其腫瘤轉移相關基因表現。第二年將研究CT26 癌症類幹細胞之腫瘤小鼠對於腫瘤生長、轉移及腫瘤微環境的致病因子及機轉。第三年，我們將給予CT26 癌症類幹細胞之腫瘤小鼠口服魚油及硒酵母，探討其對於抑制癌症幹細胞之腫瘤生長及腫瘤轉移的能力及其機制。經由上述的研究，我們希望能尋找導致癌症幹細胞的分子路徑。並且在小鼠模式上發展出有效的抗癌症幹細胞的營養素，期待將來能實際運用在癌症病人，改善癌症患者的生活品質及藥物療效。" "Although traditional cancer therapies are high efficiency to kill cancer cells, some of the advanced malignancy cells can still survive. Recent studies have shown that these small population of tumor cells, were cancer stem cells (CSCs). CSCs have the abilities to promote tumor drug-resistance and metastasis, and play an important role in cancer progression and recurrence. Colon cancer is one of the most common malignant neoplasm, which 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 will treat BALB/c mouse colon carcinoma cells (CT26) with chemotherapeutic drug- cisplatin and screen the side population cells (SP cells) in CT26 with Hoechst dye to establish and characterize a colon CSCs research model for the following experiments. Furthermore, the gene and protein expression of biomarker, tumor growth, tumor–associated inflammation, epithelial-mesenchymal transition, metastasis–associated chemokines and matrix metalloproteinases of CSC are investigated. Then, we will identify the mechanism and factors of tumor associated microenvironment exert control over tumorigenic ability, body weight loss and tumor metastasis of the CT26-CSCs bearing tumor mice. Third, we will examine the capacity of fish oil and selenium yeast combined nutrients to inhibit the capability of tumor growth and metastasis in an in vivo model of CT26-CSCs. Through all these efforts, we hope to develop effective nutritional strategies to support the need for body composition and stimulate anti-CSCs activity in the mouse model. Consequently, our study has high clinical values to investigate the effect of nutraceuticals in treating cancer stem cells."

Keyword(s)

結腸癌
癌症幹細胞
順鉑
邊群細胞
癌轉移
魚油
硒酵母
Colon cancer
Cancer stem cells
Cisplatin
Side population cells
Cancer metastasis
Fish oil
Selenium yeast

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Establishment of a Mouse Model to Assess Colon Cancer Stem-Like Cell Performance and Examine Eliminate Capacity Following Dietary Supplementation with Fish Oil and Selenium Yeast

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