根據台灣衛生福利部於2018年的統計中指出，惡性腫瘤在台灣十大死因中位居第一，子宮頸癌在台灣女性癌症排名中則位居第七。人類乳突病毒 (HPV)的感染是造成子宮頸癌的主因，初期症狀不容易被診斷出來，一旦子宮頸癌發生轉移的現象該患者之五年存活率會降低許多。而罹患子宮頸癌的女性中神經內分泌癌之發生率則位居第三，屬於罕見的子宮頸癌類型，與鱗狀細胞癌和腺癌相比是一種較為惡性的腫瘤型態。因此，為了更有效治療罕見發生的神經內分泌子宮頸癌，了解神經內分泌子宮頸癌與其他類型子宮頸癌不同的分子作用機制是重要的任務。在先前的研究中利用二維差異電泳 (2D-DIGE)與基質輔助雷射脫附游離飛行時間質譜儀 (MALDI-TOF-MS)分析神經內分泌子宮頸癌細胞 (HM-1)與其他三種子宮頸癌細胞 (Caski、ME-180、HeLa)之間蛋白質表現的差異，挑選出在HM-1細胞中具有高度蛋白表現量的Transgelin及Galectin-1作為後續研究的標的。在本研究中，使用從人類組織中分離的神經內分泌子宮頸癌細胞HM-1及HM-2，利用RNA干擾技術抑制Transgelin及Galectin-1蛋白表現量，Transgelin基因被沉默後能夠有效抑制神經內分泌子宮頸癌細胞的侵襲能力，也會導致細胞週期的停滯、促進細胞凋亡進而導致細胞增殖能力的下降，影響TGB-β/Smad路徑的訊號傳遞；Galectin-1基因被沉默後也能夠抑制神經內分泌子宮頸癌細胞的爬行能力及細胞增殖能力降低。透過本研究的結果可以知道Transgelin及Galectin-1都會影響神經內分泌子宮頸癌的爬行能力及增殖能力，針對神經內分泌子宮頸癌的檢測或是治療都是很好的蛋白標的。

According to the statistics of Ministry of Health and Welfare in 2017, malignant tumor is ranked first in ten leading causes of the death. Cervical cancer is ranked seventh in the ranking of female cancer. Infection of HPV is the main cause of cervical cancer. In the early stage, it is hard to be diagnosed. Moreover, the metastasis of cervical cancer decreases five-year-survival rates. Neuroendocrine cervical cancer is ranking on the third position. It belongs to rare type of cervical cancer and also be the more malignant cancer type, compared to squamous cell carcinoma and adenocarcinoma. In order to have a effective treatment in neuroendocrine cervical cancer, molecular mechanism is necessary to be researched. In the previous study, it performs 2D-DIGE and MALDI-TOF-MS to analyze the differentially expressed proteins in neuroendocrine cells (HM-1) and other types of cervical cancer cells (Caski, ME-180, HeLa). Transgelin and Galectin-1 are selected as the candidate proteins because of high protein expression in HM-1 cells. In this study, use small interfering RNA (siRNA) to knockdown Transgelin and Galectin-1 expression in HM-1and HM-2 which isolated from human tissue. The migration ability and proliferation ability of neuroendocrine cervical cancer cells are effectively inhibited. Also, signal transduction of TGB-β/Smad pathway is inhibited. After Galectin-1 being knockdown, it inhibits migration and proliferation in neuroendocrine cervical cancer cells. As a result, Transgelin and Galectin-1 affect the migration and proliferation ability in neuroendocrine cervical cancer. There are protein targets in detection and treatment of neuroendocrine cervical cancer.

摘要 1
Abstract 2
致謝 3
縮寫表 7
壹、文獻回顧 9
一、子宮頸癌 9
（一）、簡介 9
（二）、分期 12
二、神經內分泌子宮頸癌 (Neuroendocrine carcinoma of the cervix, NECC) 14
三、神經內分泌子宮頸癌與其他類型子宮頸癌差異蛋白之比較 18
四、Transgelin相關背景介紹以及過往研究 23
五、Galectin-1相關背景介紹以及過往研究 23
六、研究目的 25
貳、材料與方法 26
一、實驗藥品與材料 26
二、實驗細胞株與細胞培養 28
三、siRNA基因沉默候選蛋白質(Candidate protein)基因 28
四、功能性試驗 29
(一)、細胞癒合試驗 (Wound healing assay) 29
(二)、細胞遷移試驗 (Migration assay) 29
(三)、細胞增殖試驗 (Proliferation assay) 30
(四)、流式細胞儀 (Flow cytometry) 30
(五)、西方墨點法 (Western blotting) 31
參、實驗結果 35
一、 HM-1和HM-2細胞特性與型態 35
二、 Transgelin和Galectin-1在HM-1和HM-2的蛋白表現量 37
三、 Transgelin在HM-1和HM-2中的功能性試驗 38
（一）、siTAGLN濃度測試 38
（二）、Transgelin影響細胞爬行能力 40
（三）、Transgelin影響細胞增殖能力 44
（四）、Transgelin影響細胞週期進行 45
（五）、Transgelin影響細胞凋亡路徑及JNK蛋白磷酸化反應 50
（六）、Transgelin影響TGF-beta/ Smad family路徑 54
四、 Galectin-1在HM-1和HM-2中的功能性試驗 56
（一）、siLGALS1濃度測試 56
（二）、Galectin-1影響細胞侵襲能力 57
（三）、Galectin-1影響細胞增殖能力 60
（四）、Galectin-1影響細胞週期進行 61
肆、討論 63
伍、結論 70
陸、參考文獻 71
柒、補充表格 75

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