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系統識別號 U0026-2908201913375400
論文名稱(中文) 探討PTX3在抗癌藥物治療後的休眠頭頸部鱗狀細胞中的作用
論文名稱(英文) The role of PTX3 in anti-cancer drug-induced head and neck squamous cell carcinomas dormancy and metastasis
校院名稱 成功大學
系所名稱(中) 生物科技與產業科學系
系所名稱(英) Department of Biotechnology and Bioindustry Sciences
學年度 107
學期 2
出版年 108
研究生(中文) 鄭兆良
研究生(英文) Zhao-Ling Zheng
學號 L66061014
學位類別 碩士
語文別 中文
論文頁數 87頁
口試委員 指導教授-陳炳焜
口試委員-郭靜娟
口試委員-洪良宜
中文關鍵字 頭頸癌  順鉑  細胞休眠  PTX3  癌症轉移 
英文關鍵字 Head and neck cancer  cisplatin  PTX3  tumor dormancy  metastasis 
學科別分類
中文摘要 頭頸部鱗狀細胞癌(HNSCC)是世界上好發率第六的癌症。大約有百分之五十的頭頸癌患者具有化療後復發的問題。癌細胞能夠進入休眠狀態,而這些休眠的細胞由可以潛伏在病患體內數年甚至數十年之久,導致患者持續擁有復發的風險。然而,化療誘導的腫瘤休眠和轉移性復發的分子機制仍不清楚。在本篇研究中建立了順鉑處理後存活頭頸癌細胞的系統(CDDP-S)。藉由流式細胞術分析,可以看見CDDP-S細胞失去了細胞增殖的活性,並使細胞週期停滯在G1期,並看見DEC2,BMP4和NR2F1等休眠相關基因的表現量增加,表示形成腫瘤休眠。另一方面,PTX3與頭頸癌轉移相關,並在CDDP-S細胞中表現量上升。此外,順鉑處理的腫瘤細胞中PTX3的表現量增加,然而其表現卻與HNSCC中的抗藥性無關。有趣的是,順鉑治療後存活癌細胞對表皮生長因子(EGF)刺激更敏感,導致PTX3和MMPs的表現增強。此外,PTX3至弱抑制EGF處理所促進的EMT標示基因和腫瘤爬行和侵襲測能力,結果顯示順鉑處裡後存活細胞在EGF處理下獲得比一般頭頸癌細胞更強的轉移能力。這些結果表明,在休眠的CDDP-S細胞中,PTX3可以促進EGF誘導的癌轉移。
英文摘要 Head and neck squamous cell carcinoma (HNSCC) is sixth common cancer in the world. Cisplatin has been used for treatment of many human cancers including head and neck, ovarian and lung cancers. However, the anti-cancer drug resistance and metastasis are needed to be solved to improve the overall survival in patients. Long pentraxin PTX3 is the regulator of innate immune system that is also associated with tumor metastasis. Our previous studies found that the expression level of PTX3 was upregulated in anoikis resistant head and neck squamous carcinoma (HNSCC) cells. In this study, we want to clarify whether PTX3 plays a role in the regulation of drug resistance and metastasis in post-cisplatin surviving HNSCC cells (CDDP-S cells). We found that the expression of PTX3 was increased in cisplatin-treated tumor cells, however, the expression of PTX3 was not correlated with the drug resistance in HNSCC. The survival cancer cells after cisplatin treatment were more sensitive to epidermal growth factor (EGF) stimulation, resulting in enhancement of PTX3 and MMPs expression. In addition, PTX3 knockdown inhibited EMT markers in EGF-treated cells. Trans-well migration and invasion assays further indicated that post-cisplatin surviving cells acquired stronger metastatic ability in EGF-treated cells. It is worthy to note that CDDP-S cells not only reduced proliferation ability but also showed the increase of dormancy expressing molecule such as DEC2, BMP4, and NR2F1, indicating the formation of tumor dormancy. These results suggest that the increase of PTX3 may confer the sensitivity to EGF-induced metastasis in dormancy CDDP-S cells.
論文目次 中文摘要 I
英文摘要 II
誌謝 V
目錄 VI
表目錄 IX
圖目錄 X
附圖目錄 XI
縮寫表 XII
一、研究背景 1
1-1 頭頸癌及治療簡介 1
1-2 癌細胞休眠(Tumor dormancy) 4
1-3 五聚環蛋白3(Pentraxin3, PTX3)簡介 7
1-4 研究目的 12
二、實驗方法 13
2-1 細胞株 13
2-2 全細胞裂解 13
2-3 蛋白質轉漬法 13
2-4 RNA萃取 14
2-5 反轉錄聚合酶連鎖反應與即時聚合酶連鎖反應 14
2-6 報導基因轉染實驗 (Reporter assay) 15
2-7 短暫性基因致弱實驗(Transient knockdown) 15
2-8 流式細胞儀實驗(Flow cytometry) 16
2-9 實驗性肺轉移分析(Experimental lung metastasis assays) 17
2-10 細胞遷移實驗(Transwell migration assay) 17
2-11 細胞侵襲實驗(Transwell invasion assay) 17
三、實驗結果 19
3-1 建立順鉑化療後存活的頭頸癌細胞休眠系統 19
3-2 CDDP-S細胞對於EGF所調控的癌轉移更為明顯 20
3-3 CDDP-S細胞藉由誘導PTX3的表現促進癌轉移能力 22
四、討論 28
4-1 化療治療導致細胞休眠 28
4-2 表皮生長因子EGF誘導細胞休眠癌轉移 29
4-3 CDDP-S細胞藉由誘導PTX3的表現促進癌轉移能力 30
4-4 未來研究方向 32
4-5 總結 33
參考文獻 35
圖表 48
附錄 71




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