| 摘要: | 中文摘要
針對2-Phenyl-1, 8-naphthyridin-4-one (2PN)衍生物進行抗癌活性篩選。發現化合物2-(3-methoxyphenyl)-6-methyl-1,8-naphthyridin- 4(1H)-one (CYL-1)能有效的抑制人類癌症細胞的生長，包括肝癌、肺癌、乳癌、大腸直腸癌和子宮頸癌，其中CYL-1對於肝癌細胞株Hep G2達到50%的抑制濃度(IC50)近於0.14 μM。本研究主要以形態觀察、流式細胞儀分析及西方墨點法之技術，進一步探討CYL-1的抗癌作用機轉。
首先，我們從鏡檢可以觀察到肝癌細胞株Hep G2以化合物CYL-1處理後，其細胞的形態變圓以及細胞直徑增加。我們也以Propidium iodide結合到細胞DNA，利用流式細胞儀來分析CYL-1對於細胞週期的影響；結果發現經過CYL-1的處理，能促使細胞週期停滯在G2/M期，並出現細胞多倍體化。同時，我們利用西方墨點法來探討G2/M期相關蛋白質在CYL-1作用下的表現情形；結果顯示，CYL-1會造成p21的表現量增加，也會造成時間依存性之CDK1減少。
我們的結果顯示CYL-1可以抑制癌細胞的增生，並且證實CYL-1造成的細胞週期停滯與p21及CDK1有關。
英文摘要
2-Phenyl-1,8-naphthyridin-4-one (2PN) derivatives were synthesized and examined their anticancer effects toward human hepatoma (Hep G2, Hep 3B, and HA22T), lung cancer (NCI-H226, A549, and CH27), breast cancer (MCF-7), colon carcinoma (COLO 205), and ovarian cancer (HeLa) cells in our laboratory. Among these derivatives, 2-(3-methoxyphenyl)-6-methyl-1,8-naphthyridin- 4(1H)-one (CYL-1) was more sensitive to Hep G2 cells with an IC50 value approximately to 0.14 μM. Further, the action mechanisms of CYL-1 were investigated by morphological observation, flow cytometry analysis and western blot technology.
Microscopic examination showed that treatment with CYL-1 exhibited the distinct round-up shapes and an increase in cell diameter compared to polygonal shapes of control cells. Cell cycle distribution analysis indicated that CYL-1 induced G2/M arrest and following polyploid appeared. In the meanwhile, the mitotic mechanisms of CYL-1 were verified by western blot technology. The data showed that CYL-1 induced p21, and CDK1 down-regulation.
Taken together, our results indicate that CYL-1 inhibited cell growth in a time- and dose-dependent relationships. The cell cycle arrest are associated with p21 and CDK1. |
