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  • 學位論文

酵素水解果膠物協同順鉑抑制人類肺癌及肝癌細胞之研究

Synergistic antitumor effect of enzyme-hydrolyzed pectin and cisplatin against human lung cancer and liver cancer cells

指導教授 : 吳明昌
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摘要


順鉑 (DDP)為目前臨床上常使用的抗腫瘤藥物,但也伴隨著嚴重副作用,本研究主要探討酵素水解果膠物 (PET)聯合DDP對人類肺癌及肝癌細胞之影響,酵素水解果膠物聯合DDP作用A549及HepG2可抑制細胞生長且具有協同作用、改變細胞週期分布、增強細胞凋亡反應,其中DDP 12h+PET 12h 順序聯合治療組效果最好,西方墨點分析顯示PET與DDP組合處理可增強Bax、p53、p38及Caspase-3蛋白,並降低Bcl-2蛋白。更重要的是,使用PET和DDP組合處理方式可減弱DDP對於正常HEK293腎細胞誘導的毒性。我們的數據顯示,使用天然來源的PET聯合DDP處理有助於成為肺癌和肝癌的一種新輔助治療的重要方式,這也降低DDP對腎毒性和延緩DDP耐藥性的發展提供重要資訊。

並列摘要


Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of pectin enzyme treated pectin (PET) and DDP on human lung cancer A549 cells and liver cancer HepG2 cells. The combined use of PET and DDP had a synergistic effect on the growth inhibition of A549 cells and HepG2 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + PET 12 h. Western blot analyses showed that the combination treatment of PET and DDP upregulated Bax, p53, p38, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by PET and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of PET from natural sources and DDP could be an important new adjuvant therapy for lung cancer and liver cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.

參考文獻


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