| 摘要: | 吉西他濱抗藥性在治療胰臟癌病患的過程中時常發生，造成胰臟癌治療上的困難。在多種導致吉西他濱抗藥性的要素中，癌症幹細胞被認為是其中的關鍵。本研究成功建立小鼠吉西他濱抗藥性胰臟癌Panc02/GR細胞，並觀察到此細胞具較強的腫瘤生長能力與較高的癌症幹細胞標誌之mRNA表現。然而牛奶中的羥化硬脂酸有效抑制吉西他濱抗藥性胰臟癌細胞，並降低其Stat3的蛋白質表現與Sox2、c-Myc等癌症幹細胞標誌的mRNA表現。此外，蛋白質體學分析結果發現羥化硬脂酸 (590) 調節的蛋白中，主要抑制粒線體中有關能量代謝、電子傳遞鏈中複合體I與III次單元的蛋白表現。總結來說，牛奶中的羥化硬脂酸透由Stat3的抑制，改變粒線體中氧化磷酸化與能量代謝的能力，進而抑制胰臟癌幹細胞的活性，顯示其具有成為胰臟癌藥物的潛力。
Gemcitabine resistance usually happens to pancreatic cancer patients in clinical, which makes the treatment much harder. According to past research, cancer stem cell theory is thought to be the critical factor to cause gemcitabine resistance. In our study, we built the murine gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) cell, Panc02/GR cells, and proved that Panc02/GR cells conceived the characteristics of cancer stem cells like higher cancer stem cell markers expression and stronger tumorigenicity. Next step, we treated Panc02/GR cells with the hydroxy stearic acids from milk, showing that hydroxy stearic acids inhibited cell viability. Besides, the results from Western blotting and qRT-PCR demonstrated that the Stat3 protein expression and the Sox2 and c-Myc mRNA expression were also reduced by hydroxy stearic acids. Furthermore, by proteomic analysis, the hydroxy stearic acid, 590, mostly reduced the expressions of the proteins about complex I and III in the electron transport chain, TCA cycle, and ribosome in mitochondria. To conclude, the hydroxy stearic acids, especially 590, could inhibit the pancreatic cancer stem cells via mitochondrial biogenetic metabolism reduction, showing the potential as a promising anti-cancer drug. |
