Study on the Attenuation Mechanisms of Immuno-suppression and Muscle Proteolysis by Fish Oil and Selenium Yeast in Chemotherapy-Treated Lung Cancer Mice Model

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簡歷

基本資料

Project title

Code/計畫編號

NSC102-2628-B019-001-MY3

Translated Name/計畫中文名

利用肺癌小鼠模式探討魚油合併酵母硒減緩化療及癌症所導致免疫降低及肌肉蛋白質流失之機制

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=11269147

Year

2015

Start date/計畫起

01-08-2015

Expected Completion/計畫迄

31-07-2016

Bugetid/研究經費

1800千元

ResearchField/研究領域

食品科技(農)

"癌症惡病質(Cancer cachexia)為一種惡性衰弱的病症，惡病質顯著提高癌症患者的發病率及死亡率。其中，免疫受損及肌肉流失為惡病質主要的症狀，其會導致一連串的嚴重後果。導致癌症惡病質的因子，除了腫瘤本身之外，治療的手段(如化學療法)也會導致發炎及體重流失的情形出現。但目前甚少針對化學療法所導致的骨骼肌肉蛋白質分解及發炎現象做為研究探討。由於肺癌屢屢高居癌症死亡排行榜的首位，且為最容易產生惡病質症狀的癌種，因此本實驗室首先建立出肺腺癌細胞(Line-1)及其化療藥物 (docetaxel)單獨或合併所誘導惡病質之動物模式，且經臨床上所偵測惡病質的參數作為確認。利用此動物模式發現，肺癌及其化學治療藥物對於身體組成及免疫反應具有不同的影響能力。此外，結果也發現docetaxel 雖然可藉由抑制Tregs 及MDSC 來調節免疫反應，但相反的卻會對肌肉造成嚴重的副作用。因此，我們希望利用此小鼠惡病質動物模式，更進一步了解造成肌肉萎縮的機制；另外利用ω-3 脂肪酸及酵母硒等營養素的介入，來評估是否可作為改善免疫及肌肉萎縮流失的策略。本計畫的研究目的，主要是利用先前所建立的動物模式，來探討ω-3 脂肪酸及酵母硒對於減緩肌肉流失及改善免疫的能力。首先，實驗將探討單獨或合併ω-3 脂肪酸及酵母硒，是否可改善肺癌或經化療後所導致免疫失常之能力。接著，將探討肺癌及其化療藥物單獨或合併所導致骨骼肌肉受損的機制，確認其蛋白質分解路徑為何。第三，我們將嘗試利用ω-3 脂肪酸及酵母硒，探討其對於減緩肌肉降解的能力及其機制。經由上述的研究，我們希望能尋找導致癌症患者肌肉萎縮流失及免疫降低的路徑。並且在小鼠模式上發展出有效的抗惡病質的營養素，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。" "Cancer cachexia is a severe debilitating disorder, which causes significant morbidity and mortality. Impaired immune function and muscle wasting are major symptoms for cancer cachexia, leading to serious consequences. Antineoplastic therapies such as surgery, radiotherapy and chemotherapy, may also impact on the development of systemic inflammation and wasting. However, little is known about proteolysis and inflammatory events that occur in skeletal muscle with chemotherapy. Lung cancer is a leading cause of mortality worldwide and the most commonly subject seen in cachexia. Therefore, our lab established a mice model for lung adenocarcinoma or docetaxel induced cachexia, by determine clinical cachectic parameters. We have shown in a cachectic rodent model of lung cancer that lung cancer and its chemotherapy have differential capacity to interfere with body composition and immune responses. In addition, we also found that docetaxel modulated immune responses by suppressing Tregs and MDSC, but aggravation of body and muscle wasting. We believe that this validated model can be used for understanding the mechanism of muscle atrophy in lung cancer, and evaluating novel nutritional strategies (ω-3 fatty acids and selenium yeast) in preventing immuno-suppression and muscle proteolysis. The aim of the present investigation was to examine the anti-wasting and immune improvement effects of nutraceuticals such as ω-3 fatty acids and/or selenium yeast by using establishment mouse model. First, we will examine the effects of individual and/or combined nutrients on the lung carcinoma alone or with chemo drug-induced immune dysfunction. Then, we will identify the mechanism by which cachectic factors exerts control over proteolytic pathway in gastrocnemius muscle of cachectic mice. Third, we will examine the capacity of individual and/or combined nutrients to inhibit the proteolytic capability in an in vivo model of muscle wasting. Through all these efforts, we hope to develop effective nutritional strategies to support the need for body composition and stimulate anti-tumor immunity after chemotherapy in the mouse model. Consequently, it is high clinical values to investigate the effect of nutraceuticals in cancer cachexia."

Keyword(s)

癌症惡病質
化學療法
免疫降低
肌肉蛋白質流失
ω-3 脂肪酸
酵母硒
肺癌小鼠模式
Cancer cachexia
Chemotherapy
Immuno-suppression
Muscle proteolysis
ω-3 fatty acids
Selenium yeast
Lung cancer mice model

DSpace CRIS

Study on the Attenuation Mechanisms of Immuno-suppression and Muscle Proteolysis by Fish Oil and Selenium Yeast in Chemotherapy-Treated Lung Cancer Mice Model

基本資料

Description