周芬碧楊舜傑Shun-Chieh生化暨生物科技研究所2026-10-289999-12-312006https://handle.ncl.edu.tw/11296/5ub58nhttps://scholars.csmu.edu.tw/handle/123456789/35249肝癌是國人長久以來一直困擾的疾病，因為早期的不易發現也造成容易忽略，同時對於一些抗癌藥也有抗藥性的問題產生。之前的研究指出荖葉具有抗氧化的功能同時也能抑制一些癌症的產生，但是相對於肝癌的研究卻很少，因此我們想探討荖葉對於肝癌形成初期減緩其纖維化的現象及對於抗癌藥毒殺肝癌細胞的能力是否有協助的效果。在動物實驗方面，我們探討荖葉的抗氧化能力對於肝纖維化的過程中是否有扮演重要的角色，我們利用四氯化碳動物模式給予荖葉萃取液觀察肝纖維化的情形及其機制之探討：發現荖葉高低濃度對於四氯化碳所造成的肝纖維化及血液中aspartate aminotransferase (AST)、alanine aminotransferase (ALT)都有抑制的現象，同時對於體內superoxide dismutase (SOD) 、catalase (CAT) 酵素活性都有提升的現象而使老鼠體內的自由基有減少的趨勢，影響的機制則是透過TIMP2 、Ras、Raf、Erk訊息傳遞路徑使體內matrix metalloproteinase-2 (MMP2) 蛋白活化去降解alpha-smooth muscle actin (α-sma)沉積造成肝臟纖維化的減少。另外我們以荖葉萃取液處理HepG2肝癌細胞探討glutathione S-transferase (GST) isoforms表現，發現荖葉會抑制GSTα酵素表現量，再以不同抗癌藥加以處理發現在cisplatin毒殺HepG2肝癌細胞過程中有加成細胞凋亡的現象。進一步探討其加成毒殺肝癌細胞的機制中發現荖葉會抑制HepG2肝癌細胞體內GST酵素活性、multidrug resistance protein 2 (MRP2) 蛋白表現量、glutathione (GSH)濃度，其中以荖葉會抑制GSH濃度為最主要的機制。因此我們推測荖葉的護肝功能在正常生理功能下可以抑制肝纖維化的產生而在肝癌形成時又有加成一些抗癌藥毒殺肝癌細胞的能力。Hepatoma always besiege with people in Taiwan. It is not easy to diagnose in early state and some drug resistance problem. Recent research indicate that piper betel leaf (PBL) have antioxidant effect also can inhibite cancer accrue, but it is less about PBL to hepatoma research. So we want to know the effect on PBL to liver early state fibrosis and the ability of PBL in hapatoma cancer cell. In this experiment, we use CCl4 induce rat liver fibrosis to discuss the role PBL have play. We find out that PBL will decrease the AST, ALT CCl4 induce in rat liver, also increase SOD, CAT enzyme activity to decrease free radical, also effect in TIMP2, Ras, Raf signal pathway to active MMP2 enzyme expression down regulate α-sma and make the liver fibrosis more less. In hapatoma cell HepG2, we use PBL extract to confer the GST isoforms expression. PBL will inhibite GST total and GSTα activity. If treat PBL with cisplatin will increase the apoptosis effect in cell cytotoxicity. The mechanism of PBL to enhance cisplatin cytotoxicity are toward inhibite GST activity, MRP2 protein expression and GSH activity, the most major mechanism is GSH activity. So from the experiment we suggest that PBL can protect liver fibrosis in normal state otherwise can help cancer drug to kill cancer cell when cancer accrue.thesis