2013-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/644702摘要：食道癌在全球包括台灣是一個重要的癌症致死疾病。光動力療法(photodynamic therapy，PDT) 被證明為一治療早期食道癌的低侵入性有效療法。這種照光治療，是先讓癌細胞吸收一種特定的光感劑藥物，再以特殊波長的光束照射癌細胞，引發細胞毒性，摧毀癌細胞。而由Photofrin 這種最廣泛使用的光感劑引發之光動力療法．在食道癌細胞中的作用機制與耐受性產生的原因目前仍不清楚。表皮生長因子受體(EGFR)的活化與癌症治療的耐受性有極大的相關。我們觀察到EGFR 的蛋白表現在光動力治療的食道癌細胞中有大量下降的現象。因此我們假設EGFR 在光動力治療的耐受性中可能扮演重要的角色。而初步利用全基因微陣列分析，我們看到除了EGFR 之外，TNF 與EFNA1 基因也可能在參與在光動力治療的耐受性機制中。在這個計畫中，我們將針對與食道癌細胞之光動力療法耐受性相關的機制做系統化的分析。並且也將釐清EGFR， TNF 與EFNA1 於食道癌耐受細胞中扮演的角色。為了完成這些目標，我們將在未來三年中將進行事以下的研究:(1) 針對我們篩選出的高耐受性的細胞株做全基因微陣列分析，以了解食道癌細胞中參與光動力療法耐受機制的相關途徑(2) 研究在食道癌細胞中，EGFR在Photofrin引發之光動力療法之耐受性機制中扮演的角色(3) 評估EGFR與其他相關途徑之抑制劑對於增加食道癌細胞對於光動力療法敏感性之效果(4) 研究在食道癌細胞中，TNF 與EFNA1 基因在光動力療法之耐受細胞中的活化情形與相關功能這個研究將提供許多關於Photofrin引發之光動力療法在食道癌細胞中之作用機制方面的珍貴新知，並且可以更進一步了解食道癌細胞對光動力療法之耐受機制，為提高光動力療法的有效性提供新的方向。<br> Abstract: Esophageal cancer (ECa) is one of the major causes of death from cancer worldwide including Taiwan. The treatment outcome remains poor, with a 5-year survival rate ranging around 15 to 24% after treatment. Photodynamic therapy (PDT) has been demonstrated as an affective minimally invasive treatment modality for early esophageal cancer by using a photosensitizer which induces a cytotoxic photoreaction in tumor cells after exposure to a specific wave-length of light. However, the mechanismsof PDT-induced cell death as well as the resistance to PDT in ECa cells are poorly understood. EGFR activation is known to induce resistance to many anti-cancer treatments. We hypothesize that EGFR may play some roles in PDT resistance. Photofrin is a most frequently used photosentizer in PDT. We have observed that the protein expression of EGFR was drastically decreased in ECa cells under Photofrin-PDT treatment. To explore the mechanism of PDT resistance in ECa cells, we have successfully selected several PDT-resistant subcell lines from wild type ECa cells and analyzed by a whole-genome microarray. We found in addition to EGFR, the expressions of both TNF and EFNA1 genes may also participate in the mechanisms of Photofrin-PDT treatment. In the current project, we intend to further clarify the role of of EGFR as well as TNF and EFNA1 in the molecular actions of the resistance to Photofrin-PDT in ECa cells.The aims of the study in the three years to come will be:(1) To explore the cellular pathways for Photofrin-PDT resistance by analyzing the global gene expression of the selected the ECa variants those are highly resistant to Photofrin-PDT treatment.(2) To investigate the roles of EGFR in the resistance to Photofrin-PDT treatment of ECa cells.(3) To evaluate the efficacies of the inhibitors of EGFR and PDT-resistant associated pathways for sensitizing ECa cells to Photofrin-PDT.(4) To understand the function and the expression of TNF and EFNA1 in the resistance to Photofrin-PDT within ECa cells.The study will provide valuable novel information for the cellular actions of the Photofrin-PDT treatment based on the esophageal cancer cell model. Additionally, it provides an insight to improve the efficacy of PDT through understanding the molecular mechanisms of Photofrin-mediated PDT-resistance.食道癌光動力療法表皮生長因子受體Esophageal cancerPhotodynamic therapyEGFR