- 學位論文
沒食子酸(Gallic acid)干擾Small GTPase, Ras/PI3K及Ras/ERK路徑抑制人類胃癌細胞的轉移能力之作用
Gallic acid Inhibits Human Gastric Carcinoma Cell Metastasis via Interfering Small GTPase, Ras/PI3K and Ras/ERK Signaling Pathways
摘要
摘要: 胃癌仍是全世界癌症的第四名，雖然內視鏡診斷工具的長足進步，早期胃癌的治癒率已達到95％，胃癌的轉移仍是晚期胃癌無法治療的主要原因。多酚大量存在於日常蔬果中，類黃酮及酚酸為多酚常見之成份，大多數研究集中於類黃酮抑制多種惡性癌細胞的成長及抗氧化作用，而對於酚酸的研究不多。酚酸巳知具有抗氧化作用, 促成癌細胞凋亡，細胞週期停滯。本實驗經由細胞毒性試驗，0.01mM的gallic acid 可達到4mM protocatechuic acid濃度的效果，在傷口癒合（wound healing assay）、Boyden chamber分析的結果中，顯微鏡下都發現明顯抑制的現象，進一步用Zymography assay，2.0μM低濃度的gallic acid對於MMP2/9蛋白的分泌有明顯抑制的作用, MMP2/9的抑制現象有可能是透過抑制FAS（Fatty acid synthase）的表現，進而降低了AGS癌細胞中NF-κB的活化，另外磷酸化FAK以及RhoA、Rac-1、cdc42、Ras，這群調節細胞貼付與細胞骨架組裝的相關蛋白，表現也受到了gallic acid（GA）的抑制。顯示gallic acid （GA）確能有效抑制AGS細胞轉移，也許gallic acid （GA）未來可以用於臨床預防及治療胃癌的轉移。
並列摘要
Abstract : Gastric cancer is still the fourth front of the cancer in the world。Although by the progression of endoscopic examination technology，the curative rate of early gastric cancer has been reached up to 95%，but metastasis of late-stage gastric cancer is still been the major problem of treatment。Polyphenols in fruit and vegetables are natural antioxidants that are assumed to contribute to be the prevention of cardiovascular disease and malignancy。The most abundant types of polyphenol in the human diet are the flavonoids and phenloic acids。Although many studies have been carried out to investigate the chemoprevention role of flavonoids ， much less attention has been focused on phenloic acids 。 Actually, the cytotoxicity possesses of phenloic acid has the ability to against cancer cells，anti-inflammatory and antimutagenic properties。 In our study， 0.01 mM gallic acid has the same effect of cell toxicity compared with protocatechuic acid with 4.0 mM concentration。By the analyze of wound healing assay and Boyden chamber results，gallic acid has powerful effect on the inhibition of AGS cell。The activity of MMP2/9 of AGS cell were note been obvious inhibited by 2.0μM Gallic acid through Zymography assay。Gallic acid may control the activity of MMP2/9 through Fatty acid synthase， an inhibitor of NFκB。Multiple proteins involved in metastasis and cytoskeleton reorganization signal pathway including Ras、RhoA、Rac-1、Cdc42、RhoB, PI3K，p38MAPK was analyzed by western blot，gallic acid also has inhibitory efficacy on them。Immunoreactivity assay of AGS cell F-actin treated by gallic acid showed inhibitory effect on AGS cell migration。For all the reasons, we believe that gallic acid may be an effective material for prevention and treatment of the gastric cancer in the future。