乳酸菌GG對化療藥物5-氟尿嘧啶誘導人類腸上皮細胞發炎之調節
作用

抗癌藥物是常引起系統性免疫抑制及腸道受損，如5-氟尿嘧啶(5-FU)是常見的化療藥物，在臨床上是毒殺腸胃道癌症有較好的治療效果，但常見之副作用為噁心、嘔吐及腹瀉導致體重減輕，嚴重時易引發免疫發炎反應與相關併發症，及抗藥性等問題。化療藥物在對抗癌細胞的同時，也破壞了正常腸道結構，造成腸道黏膜炎，腹瀉等副作用發生，因此在這情況下，發展解決因化學治療製劑產生的副作用是必須的。在過去對於腸胃道疾病的治療，乳酸菌一直被受到注意，因為乳酸菌本身是可促進或減緩腸道的防禦系統功能，如免疫調節作用、免疫減緩作用和免疫排斥反應，且具有抗發炎、調整腸道完整度，以及調控過敏反應等。因此，在這項實驗中，利用化療藥物5-氟尿嘧啶(5-FU)誘導Caco-2細胞損傷產生發炎反應，並分別以活菌與85℃, 20分鐘的死菌加入於5-FU 誘導Caco-2細胞上的作用，調控發炎反應的能力。初步實驗結果顯示，以2、4小時，MOI=25的活菌與死菌(85℃, 20分鐘)進行毒性分析後，其具有良好生物相容性。最後由基因表現量的結果顯示，經過活菌與死菌經過2小時的作用下，IL-12、TNF-α、MCP-1之mRNA都有明顯向上調控的趨勢；經過4小時的作用，活菌與死菌之間的發炎反應量沒有像在2小時的作用下表現量這麼高，其原因可能是因為在4時間的作用下細胞似乎隨著時間的延長受到不同型式乳酸菌的影響促進的發炎反應趨勢會緩緩向下調控。

關鍵字

5-氟尿嘧啶；乳酸菌GG ；發炎

並列摘要

Many anti-cancer medicine usually cause system immune inhibition and impaired gut, such as 5-Fluorouracil (5-FU) is a common chemotherapy drug. 5-FU cytotoxicity in clinical gastrointestinal cancers is better therapeutic. It still has common side effects which are nausea, vomiting and diarrhea lead to body weight lose. Chemotherapy drugs also damage the normal intestinal structure, causing intestinal mucous, diarrhea and other side effects occurred in the fight against cancer at the same time. It is impassion serious inflammation and immune-related complications and drug resistance. It’s necessary to reduce side effect of immune inhibition. Therefore, in this case, it’s necessary that development to solve side effects of chemotherapy drugs. In the past, for the treatment of gastrointestinal diseases that lactobacilli has been received attention, because lactobacilli can promote or slow down the intestinal defense system functions, such as immune regulation immune to slow down the role of immune rejection, and has anti-inflammatory, regulate intestinal integrity, and regulation of allergic reactions. In this study, Caco-2 cells were induced inflammatory response by 5-FU and were treated with the live LGG or heat killed LGG (at 85℃ for 20 min) thereafter the effect to regulate inflammatory responses. These data showed the live LGG and heat killed LGG at an MOI of 25 for 2 and 4 hours treating times that exerted good biocompatibility via the cytotoxicity test. The results of gene expression indicated that after 2 hours live LGG and heat killed LGG treatment, the mRNA expression of IL-12, TNF-α, MCP-1 were significantly up-regulation; after 4 hours treatment, expression of these inflammatory mRNA were lower than 2 hours treatment. We considered, the host cells may be influenced by different types of LGG under 4 hours treatment and inflammatory response was slightly down-regulated.

並列關鍵字

5-Fluorouracil ； Lactobacillus rhamnosus GG ； inflammation

參考文獻

1. 行政院衛生署，中華民國九十九年台灣地區十大死因統計結果, 2010

2. Muehlbauer, P. M., Thorpe, D., Davis, A., Drabot, R., Rawlings, B. L., Kiker, E. “Putting evidence into practice: evidence-based interventions to prevent, manage, and treat chemotherapy- and radiotherapy-induced diarrhea.” Clin J Oncol Nurs vol.13, 2009, pp.336-341.

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乳酸菌GG對化療藥物5-氟尿嘧啶誘導人類腸上皮細胞發炎之調節作用

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