Study on the Mechanisms of Attenuation of Muscle Proteolysis and Immune Impairment by Nutraceuticals Intervention after Chemotherapy in Tumor-Bearing Mice

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Project title

Code/計畫編號

NSC101-2313-B019-010

Translated Name/計畫中文名

探討營養素減緩化療及癌症所導致肌肉蛋白質及免疫受損之機制

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=2635054

Year

2012

Start date/計畫起

01-08-2012

Expected Completion/計畫迄

31-07-2013

Bugetid/研究經費

1040千元

ResearchField/研究領域

食品科技(農)

"癌症為全球的主要死因一，又癌症所引起的惡病質(Cachexia)為癌症病人死亡的主要原因。其中最明顯的症狀為體重減輕、肌肉組織的耗損及免疫降低。化療的目的主要是在於殺滅癌細胞達到治癒的效果，但由於是以藥物毒殺癌細胞的方式來治療，對正常的細胞也會造成傷害，導致種種副作用的發生。因此，找出由癌細胞或化療本身所導致的肌肉蛋白質分解及免疫降低之機制，將有助於往後尋找降低肌肉受損及改善癌症病人免疫能力之策略。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，但尚無肺癌惡病質動物模式，目前我們實驗室已成功地建立了肺腺癌細胞(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。因此在本研究計劃中，我們將利用此小鼠惡病質動物模式，來研究及開發不同營養素對於減緩肌肉蛋白質受損及改善免疫功能之能力及機制。實驗首先探討肺癌及其化療藥物單獨或合併所導致肌肉受損的機制，確認其蛋白質分解路徑為何。然後，再探討肺癌及其化療藥物單獨或合併對於免疫系統的影響，比較兩者降低免疫力的機制為何。第三，我們將嘗試利用四種營養素(ω-3 脂肪酸、酵母硒、EGCG、樟芝)，探討其對於減緩肌肉降解的能力及其機制。第四，我們將嘗試營養素，增強免疫的效果，以期產生更好的抗癌免疫能力。經由上述的研究，我們希望能尋找導致癌症患者肌肉萎縮及免疫降低的路徑。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 is one of the leading causes of death in the world. Cachexia is a complex disorder characterized by progressive loss of weight, alterations in immune function and directly compromises the quality of life of cancer patients. The ultimate goal of chemotherapy is to cure cancer, allowing recovery to ensue. Unfortunately, nonspecific cytotoxicity resulting from chemotherapy remains to be a serious complication during the treatment of cancer. Therefore understanding the muscle proteolytic and immune impairment mechanisms responsible for cancer itself or its chemotherapy were essential in developing therapies to reduce muscle wasting and enhance recovery from cancer cachectic patient. Lung cancer is a leading cause of mortality worldwide and the most commonly subject seen in cachexia. However, there is no research focus on lung cancer and its chemotherapy induced cachexia. Our lab already established an animal model for lung adenocarcinoma or docetaxel induced cachexia, by determine clinical cachectic parameters. The aim of the present investigation was to examine the anti-wasting and immune improvement effects of some nutraceuticals such as ω-3 fatty acids, selenium yeast, EGCG, Antrodia camphorate by using establishment animal model. First, we will identify the mechanism by which cachectic factor exerts control over proteolytic pathway in tumor and/or chemotherapy induced muscle atrophy. Then, we will investigate the mechanism of immune suppression during tumor progress and/or chemotherapy. Third, we will examine the capacity of four nutraceuticals (ω-3 fatty acids, selenium yeast, EGCG, Antrodia camphorata) to inhibit the proteolytic capability in an in vivo model of muscle wasting. Fourth, we will test the capability of four nutraceuticals on immune enhancement. Through all these efforts, we hope to develop an effective nutraceuticals 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)

惡病質
肌肉萎縮
免疫降低
ω-3 脂肪酸
酵母硒
EGCG
樟芝
cachexia
muscle atrophy
immune impairment
ω-3 fatty acids
selenium yeast
EGCG
Antrodia camphorate

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Study on the Mechanisms of Attenuation of Muscle Proteolysis and Immune Impairment by Nutraceuticals Intervention after Chemotherapy in Tumor-Bearing Mice

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