- 學位論文
探討槲皮素對於肺癌細胞株H1355細胞生長的影響
The Effect of Quercetin on Cell Growth of Lung Cancer Cell Line H1355
摘要
槲皮素（quercetin）屬於黃酮類化合物衍生物的一種多酚類抗氧化物，存在於日常食用的蔬果中。許多文獻指出quercetin具有抗氧化、抑制發炎反應、腫瘤細胞的增生，並且促使腫瘤細胞進行細胞凋亡的效果。由於肺癌細胞與quercetin兩者之間的相關研究較為鮮少，於是本篇實驗想要探討quercetin對於肺癌細胞株H1355細胞生長的影響。首先分別以quercetin和cisplatin單獨處理H1355細胞 24和48小時，經由MTT assay分析，結果顯示quercetin在50μM會抑制細胞生長，但是cisplatin＞8 μg/mL處理則有抗性的現象發生。另外將兩者合併處理發現cisplatin無法加強quercetin所造成細胞抑制生長的效果。在細胞週期調控方面，quercetin單獨處理會使細胞週期停滯在S時期，經由Western blotting和RT-PCR分析發現，cyclin D和P21表現會增加，14-3-3σ、P53和P16並不會受到影響。另外，在細胞凋亡方面， quercetin處理會造成DNA斷裂成階梯狀片段，而且在mRNA層次發現，Bax表現量增加，Bcl-2的表現量減少；以蛋白質層次發現，pro-caspase3、Bcl-2和磷酸化Akt蛋白的表現都會有下降的現象。綜合本論文的實驗結果顯示，quercetin會抑制肺癌細胞的生長而且會透過caspase依賴性路徑導致細胞凋亡。
並列摘要
Quercetin is a phenolic natural antioxidant of flavonoids derivative, particularly abundantly among vegetables and fruits. In prior studies, quercetin has been shown to have diverse biological activities, including anti-oxidant, anti-inflammatory, anti-carcinogenic and apoptosis effects. However, the in vitro effect and detailed mechanism of quercetin in lung cancer were still unclear. In this study, human lung cancer cell line, H1355, was chosen to be treated with quercetin to evaluate the drug’s effect on cancer cell growth. Cell viability was significantly decreased by quercetin treatment in a time- and dose-dependent manner, however, resistance to cisplatin treatment was observed when the concentration cisplatin was over 8μg/ml. Co-treatment of cisplatin and quercetin did not cause any synergic effect. Flow cytometry studies for the cell cycle distribution showed that quercetin induced S-phase arrest. Based on the results of RT-PCR and Western blot analysis, our results indicated that quercetin treatment increased expression of cyclin D and P21, while the expressions of 14-3-3σ、P53 and P16 were not affected. We found that the inhibition of cell growth was accompanied by apoptosis, evidenced by gel electrophoresis of DNA fragmentation. In addition, the apoptotic effect was associated with the activation of Bax and downregulation of pro-caspase3, Bcl-2 and Akt-phosphorylation. In conclusion, quercetin may suppress proliferation of lung cancer and trigger apoptosis through caspase-dependent pathway.