- 學位論文
咖啡酸苯乙酯抑制口腔癌細胞轉移和侵襲研究
Inhibitory effects of Caffeic Acid Phenethyl Ester on Oral Cancer Cell Metastasis and Invasion
摘要
咖啡酸苯乙酯 ( caffeic acid phenethyl ester, CAPE ) 分子式為 C17H16O4 ，是蜂膠內主要活性成分之一。目前已經被證實具有抗發炎、抗氧化活性、抗病毒及抑制癌細胞生長等活性。在口腔癌方面，目前僅知 CAPE 在高濃度下會造成口腔癌細胞死亡，而 CAPE 是否可抑制口腔癌細胞株的侵襲與轉移，以及其在口腔癌細胞株內的分子機制，目前仍不清楚。本論文的目的在探討 CAPE 對於口腔鱗狀細胞癌細胞株 SCC-9 侵襲能力的影響與機制。結果顯示， CAPE 在無細胞毒殺濃度下 (0 μM to 40μM) ，會減弱 SCC-9 轉移與侵略性。西方墨點法與明膠酶譜分析更進一步發現， CAPE 會減低基質金屬蛋白酶-2 ( matrix metalloproteinase-2，MMP-2 ) 的表現與其酵素活性。 因為 CAPE 有抑制 MMP-2 表現的能力，所以對其抑制因子tissue inhibitor of metalloproteinase-2 (TIMP-2) 有活化與正調控的效果。同時也會減低focal adhesion kinase ( FAK ) 的磷酸化，以及其下游 p38/MAPK 與 JNK 等的磷酸化。 實驗結果的資料顯示，CAPE可能可以作為預防或治療口腔癌轉移的化學治療製劑。
並列摘要
Caffeic acid phenethyl ester (CAPE), an active component extracted from honeybee hives, exhibits anti-inflammatory and anticancer activities. However, the molecular mechanism by which CAPE affects oral cancer cell metastasis has yet to be elucidated. In this study, we investigated the potential mechanisms underlying the effects of CAPE on the invasive ability of SCC-9 oral cancer cells. Results showed that CAPE attenuated SCC-9 cell migration and invasion at noncytotoxic concentrations (0 μM to 40μM). Western blot and gelatin zymography analysis findings further indicated that CAPE downregulated matrix metalloproteinase-2 (MMP-2) protein expression and inhibited its enzymatic activity. CAPE exerted its inhibitory effects on MMP-2 expression and activity by upregulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and potently decreased migration by reducing focal adhesion kinase (FAK) phosphorylation and the activation of its downstream signaling molecules p38/MAPK and JNK. These data indicate that CAPE could potentially be used as a chemoagent to prevent oral cancer metastasis.