| Abstract: | 胰臟癌，又被譽為“安靜的殺手”，是近幾個年代以來最致命的癌症致死死因之一，其5年存活率依然少於10%。根據GLOBOCAN於2018年的調查顯示，胰臓癌是全球第七癌症致死之因，在台灣則是第八大癌症死因。化療是胰臓癌最常使用的診療方式，而Gemcitabine（健澤）則是胰臓癌的標準第一線治療藥物之一。然而，化療藥的使用總是會伴隨著各種副作用。有鑒於之前的研究發現，微生物相具有輔助胰臓癌之惡化或緩解之影響力，我們將於本次研究中探討益生菌合併化療藥之使用影響，以及是否能改善化療的副作用。我們使用 LSL-KrasG12D-Pdx1-Cre 轉基因小鼠作為胰臓癌研究的動物模式。將小鼠於12週齡大時注射雨蛙素來誘發胰臓炎以加速胰臓癌的發展，再給予不同劑量之化療藥健澤治療，並合併餵食不同劑量與比例之益生菌。單一接受化療藥治療之小鼠有明顯的體重下降，且從組織切片中可觀察出較大的癌化範圍，較嚴重的惡化程度、纖維化程度以及上皮間質轉換的狀況；彰顯了化療藥的副作用。 然而，在餵食益生菌(GMNL133:GMNL89 以 1:1/10 比例)之後，小鼠體重不僅有回升的趨勢，胰臓癌病變程度、惡化程度、纖維化程度（Vimentin）以及分裂中的細胞（Ki67）狀況都有顯著的改善。除此之外，血液生化值中的AST 以及ALT 都有下降的趨勢，而血小板的比率也有回升。整體而言，我們的研究結果表明，化療藥合併使用益生菌有助於減緩化療副作用，且有助於整體的治療效果。
Pancreatic cancer has remaining one of the most lethal cancer-related death for decades, its 5-year survival rate is remaining less than 10%. It was ranked the 7th leading cause of cancer death globally; while ranked the 8th in Taiwan. Chemotherapy thereby is the most common treatment for pancreatic cancer, and gemcitabine is the standard first-line treatment for advanced pancreatic cancer. However, chemotherapy always comes along with side effects. Having an image from the previous study which reveals that microbiomes can perturb the progression of pancreatic lesions in a vice-versa manner, we hereby explore the effect of the combination of gemcitabine with probiotics on chemotherapy and its side effects. Taking LSL-KrasG12D-Pdx1-Cre transgenic mice as our pancreatic cancer model, animals were first given caerulein injection to induce pancreatitis for promoting pancreatic cancer development, then receive gemcitabine and/or with oral administration of probiotics in different dosages. With biomarkers such as a decrease in body weight, deterioration in the morphology of pancreas, increased epithelial-to-mesenchymal transition (Vimentin) and cell proliferation (Ki67) degree, it reveals the side effects chemotherapy give rise to in animal model. However, along with administration of probiotics (GMNL133:GMNL89 in 1:1/10 ratio), animals show increases in body weight, significant decreases in lesion area and pathological grades, decreased Vimentin expression, decreased Ki67 expression, and improved biochemistry analysis such as decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) level, so as increased platelet cells percentage. Taking together, our results suggest that supplementation of probiotics along with chemotherapy treatment might help to ease the side effects, while in another hand, help to improve the outcome of treatments. |
