探討薑黃素在人類大腸癌HT-29細胞之抗癌作用

Abstract

台灣衛生福利部公告，大腸癌為102年台灣癌症十大死因第三位。癌症發展過程之生物機轉複雜，現行療法無法根除癌細胞且有副作用、復發率高，因此尋找有效替代療法是非常重要的。薑黃素（Curcumin）具有低細胞毒性、多目標阻斷路徑、抑制癌症發展的特性。文獻指出，細胞凋亡、細胞自噬、發炎因子NF-B和致癌基因Aurora-A kinase之間具有相關性。本研究在於探討薑黃素對HT-29細胞週期的影響、細胞凋亡與細胞自噬的現象及NF-B與Aurora-A kinase相關蛋白的影響。結果顯示，薑黃素增加促凋亡蛋白caspase 3、細胞自噬蛋白LC3-II表現量，代表HT-29啟動細胞凋亡與細胞自噬，抑制細胞生長。NF-B相關蛋白實驗顯示細胞中IB、phospho-IB及細胞核中NF-B蛋白量顯著下降。流式細胞儀分析觀察到薑黃素增加酸性囊泡比例，使用BAF抑制細胞自噬，降低薑黃素引起酸性囊泡比例的增加。整體而言，薑黃素影響HT-29細胞週期、引發細胞凋亡及細胞自噬、抑制HT-29細胞生長，並抑制NF-B路徑及Aurora-A相關蛋白的表現；BAF的使用可降低薑黃素引起的細胞自噬。

According to the report from the Ministry of Health and Welfare, Taiwan, 2013, human colorectal cancer is the third-leading cause of cancer death in Taiwan. Due to the complexity and high recurrent rate of cancer, as well as side effects of cancer treatment, improvement in chemotherapeutic regimens is urgently needed. Curcumin, safe in human, regulates multiple pathways to inhibit tumor progression, such as apoptosis, autophagy, inflammatory factor NF-B and oncogene Aurora-A. This study was proposed to investigate the effect of curcumin on cell cycle, apoptosis, autophagy, and protein expression and activity of NF-B and Aurora-A using human colorectal cancer HT-29 cells. The results showed that curcumin increased the expression of pro-apoptotic protein caspase 3 and autophagy protein LC3-II, suggesting that curcumin induced apoptosis and autophagy. Significant decline of IB and phospho-IBin whole cell lysates and NF-B in the nuclei were observed. Flow cytometric analysis found that the proportion of acidic vesicles increased in curcumin-treated HT-29 cells. Administration of BAF reduced curcumin-induced increment of the proportion of acidic vesicles. Overall, curcumin changed cell cycle, triggered apoptosis and autophagy, inhibited the growth of HT-29 cells, and inhibited expression of NF-B and Aurora-A. The use of BAF reduced curcumin-induced autophagy.