蘇純立Su, Chun-Li徐漫袁Hsu, Man-Yuan2022-06-082026-08-262022-06-082021https://etds.lib.ntnu.edu.tw/thesis/detail/efcf4288efb59bf23a1c37de58f32e4a/http://rportal.lib.ntnu.edu.tw/handle/20.500.12235/118609胰臟癌佔國人十大癌症死因第八位，胰臟癌患者死亡率十分顯著，五年生存率低於10%，因胰臟癌對藥物阻抗性增加，目前臨床沒有化療藥物可以達到良好的治療效果。與正常細胞相比，癌細胞中傾向堆積鐵。鐵依賴型細胞死亡（ferroptosis）是鐵依賴性的脂質活性氧（lipid ROS）堆積，而誘導的細胞死亡形式，其降低癌症抗藥性的特點可作為治療上的新契機。實驗證實，在BxPC3（gemcitabine抗性）而非 PANC-1（非gemcitabine抗性）中，curcumin可能藉由鐵蛋白自噬（ferritinophagy）的形式釋出游離鐵，增加游離鐵池與脂質氧化物的生成，調節BxPC3鐵依賴型細胞死亡。並且curcumin引發的鐵依賴型細胞死亡，可以增加臨床藥物gemcitabine的藥物敏感度。因此，本研究認為，利用curcumin誘導胰臟癌細胞，游離鐵增加與脂質過氧化生成，促進鐵依賴型細胞的死亡途徑，可以逆轉胰臟癌細胞對gemcitabine的抗藥性，並且有助於改善目前胰臟癌的臨床困境。Pancreatic cancer accounts for the eighth of the top ten cancer deaths in Taiwan. The mortality rate of patients with pancreatic cancer is significantly high, and the five-year survival rate is less than 10%. Due to the increased resistance of pancreatic cancer to drugs, there is no effective treatment currently. Compared with normal cells, cancer cells are more dependent on iron. The iron overload of cancer cells is beneficial to induced ferroptosis which is caused by iron-dependent lipid reactive oxygen species (lipid ROS) accumulation. Induction of ferroptosis on drug-resistant pancreatic cancer cells may be a new opportunity for treatment. Indeed, curcumin-induced ferroptosis, regulated by ferritinophagy, occurred concurrently with increased labile iron pool and lipid peroxidation in BxPC3 (gemcitabine resistance) instead of PANC-1 (non-gemcitabine resistance). Curcumin-induced ferroptosis also enhanced the sensitivity of the gemcitabine. Therefore, addative of curcumin reverse the resistance of pancreatic cancer cells to gemcitabine could improve the current clinical dilemma of pancreatic cancer.胰臟癌薑黃素鐵依賴型細胞死亡鐵蛋白自噬游離鐵池脂質過氧化物吉西他濱pancreatic cancercurcuminferroptosisferritinophagylabile iron poollipid peroxidationgemcitabine學術論文