戊醯基左旋肉鹼以及N-acetyl-Ser-Asp-Lys-Pro 具有促進胰臟癌發展的潛能

Abstract

胰臟癌是癌症死亡的主要原因之一，其預後非常不佳的理由是因為缺乏早期檢測的生物標記物以及有效的治療選項，胰臟癌的五年存活率僅僅只有8%。我們實驗室發現與健康的人們相比，在胰臟癌病患的檢體中valeryl-L-carnitine (C5)以及N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) 有著大量的表現量。C5 是一種與大多數生物代謝相關的胺基酸衍生物，透過脂肪酸氧化以及檸檬酸循環的過程，C5可以轉換成乙醯輔酶A (acetyl-CoA)進而產生細胞所需的能量三磷酸腺苷(ATP)。而擁有抗纖維化作用的AcSDKP則是一條具有四個胜肽的胜肽鏈，AcSDKP是由 prolyl oligopeptidase (POP)切掉thymosin β4 (Tβ4)的N端產生而成；AcSDKP已經被發現有能力去調控細胞增生以及血管新生等等，而臨床研究也指出AcSDKP在各種不同型態的惡性腫瘤中有極高的表現量。為了探討C5和AcSDKP是否會影響胰臟癌，我們將C5和AcSDKP加進胰臟癌的細胞株，細胞存活率分析試驗(MTS assay)的結果顯示C5和AcSDKP會使胰臟癌細胞株Panc-1及AsPC-1的細胞增長率增加，另外，C5和AcSDKP也會調況與增生相關還有與細胞凋亡的mRNA以及蛋白質的表現量；AcSDKP 甚至可以降低上皮細胞標記物E-cadherin的mRNA1表現量，並且提高間質細胞標記物Vimentin以及與上皮間質細胞相互轉換(Epithelial-Mesenchymal Transition)相關的轉錄因子Snail2的表現量。我們認為C5和AcSDKP具有促進胰臟癌發展的潛能。

Pancreatic cancer is one of the leading cause of cancer death. It carries a dismal prognosis because of lacking the biomarkers for early detection and effective therapeutic options. The 5-year survival rate of pancreatic cancer is only 8%. Our laboratory found out that both valeryl-L-carnitine (C5) and N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) have a high-level expression in pancreatic cancer patients. C5 is a kind of amino acid derivatives which involved in metabolism in most mammals. It can convert into acetyl-CoA to produce usable chemical energy ATP through β-oxidation and TCA cycle. Anti-fibrotic peptide AcSDKP is a tetrapeptide generated from N-terminal of thymosin β4 (Tβ4) by prolyl oligopeptidase (POP). It has been found that this peptide had the ability to regulate cell proliferation and angiogenesis. Clinical studies also showed that AcSDKP overexpresses in many different types of malignant tumors. To investigate whether C5 and AcSDKP have an influence on pancreatic cancer, we treated pancreatic cancer cell lines with C5 or AcSDKP. With MTS assay, we revealed that both C5 and AcSDKP would promote proliferation rate of pancreatic cancer cell lines, Panc-1 and AsPC-1. They also regulate the expression of proliferation-related and apoptosis-related mRNA and protein. Moreover, AcSDKP was shown that it can decrease the mRNA level of E-cadherin and increase the mRNA level of Vimentin and Snail2. We conclude that C5 and AcSDKP have the potential for promoting the development of pancreatic cancer.