2011-08-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/658530摘要：肝細胞癌(HCC)是一種預後極差且是國內造成癌症死亡的重要原因之一。外科手術雖可以達成最好的治療效果，但是卻非最完整的治療照顧範圍。外科手術往往只能針對一小部份的病人(約20%~30%)。肝內轉移容易造成腫瘤早期復發，因此預後極差。大部分病人會死於手術後短期間內再發或更嚴重的腫瘤出現。所以尋找跟腫瘤轉移相關的基因，便能幫助癌症治療的策略擬定。在我們先前的研究中發現，stathmin 的表現與肝細胞癌的轉移有關，並且可以成為一個預後因子，以及腫瘤早期復發的預測因子。為了瞭解stathmin 在肝細胞癌發展的過程中扮演那種角色，我們以stathmin RNAioligonucleotides 轉染進入肝細胞癌細胞株(Ha22T, HuH7/VGH, 與HCC36)並且使得stathmin 蛋白表現亮明顯減少，然而細胞生長速率卻沒有改變。不過stathmin 的表現與高期別具血管侵犯的腫瘤有高度相關，這促使我們進一步探求stathmin 與腫瘤細胞移動與侵犯的相關性。有趣的是，當stathmin 蛋白被減少後，Ha22T 與HuH7/VGH 細胞的轉移與侵犯能力也跟著下降。同時間Raf, Mek,與Erk 訊息傳導蛋白的磷酸化蛋白也跟著下降，代表這個訊息傳導訊號活性下降。然後這個Raf-Mek-Erk 訊息傳導路徑與stathmin之間的關係則需更進一步研究。<br> Abstract: Hepatocellular carcinoma (HCC) has a very poor long-term prognosis and is the leading causeof death caused by cancer in Taiwan. Surgical operation will be the most completed treatmentfor cure; however, this is not a comprehensive strategy. Surgery is curative in only a minority(about 20 to 30%) of patients. Intrahepatic metastases result in the early tumor recurrences(ETR), and hence poor prognosis. Most patients die from locally advanced or metastaticdiseases within a relatively short period of time. Therefore, to identify target genes formetastasis will help to the development of novel therapeutic intervention. In our previousinvestigation, stathmin (STMN1) expression correlates with metastatic potential, is animportant prognostic factor for HCC, and may serve as a useful marker to predict ETR. Todetermine the role of stathmin in tumorigenesis, we transfected stathmin RNAioligonucleotides into hepatoma cells (HuH 7/VGH, Ha22T, and HCC36 cells) and decreasedstathmin protein levels dramatically. However, cell growth rate in these hepatoma cells didnot change. Nevertheless, the stathmin expression closely to high stage with vascular invasionHCC, This finding enforce us to further in verstigate the role of stathmin inf cell migrationand invasion. Interestingly, the ability of in vitro cell migration and invasion in HuH 7/VGHand Ha22T cells are decreased when stathmin expression is downregulated. Moreover, theactivity of Raf, Mek, and Erk are repressed represented by decrease of the phosphorylationstatus. In conculssion, stathmin inhibition, comes with downregulation of Raf-Mek-Erk signalpathway ,resulted in reduction of tumor cell migration and invasion in HCC cell lines.However, the relationship of stathmin with tumour cell migration and invasion in HCC needsfurther investigation.Stathmin肝癌侵犯轉移StathminHepatocellular carcinomainvasionmetastasis