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研究生(外文):Wen-Ser Tseng
論文名稱(外文):Anti-proliferation and radio-sensitizing effect of caffeic acid phenethyl ester on human Daoy medulloblastoma cell line
指導教授(外文):Jen-Hwey ChiuTai-Tong Wong
外文關鍵詞:caffeic acid phenethyl estermedulloblastomaanti-proliferationradio-sensitization
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髓母細胞瘤 (Medulloblastoma)是最常見的兒童小腦惡性腫瘤。不管使用手術切除、化學治療、放射治療,其預後都不佳,因此為了提升治療的結果及降低治療方式所造成的傷害,尋找新的治療方法或藥物是目前努力的方向。蜂膠主成份之一的咖啡酸苯乙酯(caffeic acid phenethyl ester; 以下簡稱CAPE),已被證實具有抗發炎、毒殺腫瘤細胞和放射增敏等生物活性及藥理作用。
本研究之目的在於探討CAPE對人類髓母細胞瘤細胞株-Daoy的抑制生長及放射增敏之作用。本實驗以CAPE處理Daoy細胞,由MTT assay及Trypan blue exclusion assay的結果,發現隨著時間及濃度的增加可抑制Daoy細胞的增生。由分流式細胞儀實驗結果發現,隨著處理CAPE濃度的增加,會造成在G2/M phase的細胞數減少,S phase的細胞數增加。此結果顯示CAPE可延遲細胞從S phase進入G2/M phase。而由Western blot分析,CAPE對細胞週期的蛋白質的影響,可能是透過降低cyclin B1的表現來調控的。此外,當於放射照射前,先以0.1~10μM CAPE處理細胞24小時,可明顯降低細胞在放射照射後的存活。Daoy細胞處理0.1、0.3、1、3μM CAPE,其37%存活率的放射線增敏感(SER)分別為1.19、1.32、1.50、2.04。
Medulloblastoma (MB) is the most common malignant cere- bellum tumor in children. Despite surgical eradication, chemotherapy and radiotherapy, the prognosis of MB is poor. To improve current treatment prognosis in MB patients, the discovery of novel therapeutic agents become a urgent issue. Caffeic acid phenethyl ester (CAPE), an active component of propolis, is known to have antioxidant, anti-inflammatory, antiviral, reperfusion injury prevent, anticancer and radio-sensitizing effects.
This study is aimed to investigate the effect of anti-proliferation and radio-sensitization of CAPE on MB Doay cell line. Our data show that CAPE inhibited the growth of Daoy cells in a time- and concentration-dependent manner by MTT assay and Trypan blue exclusion assay. Flow cytometry assay revealed that treatment of Daoy cell with CAPE significantly decreased the percentage of G2/M fraction, and increased the S phase fraction. The results suggest that CAPE delay cell cycling from S to G2/M phase. Furthermore, Western blot analysis could demonstrate a down-regulated cyclin B1 protein expression in CAPE-treated Daoy cells. Furthermore pretreatment with 0.1~10μM CAPE markedly decreased the survival of irradiated Daoy cells. The SERs at 37% survival were 1.19、1.32、1.50、2.04 in Daoy cells for 0.1, 0.3, 1, 3μM CAPE, respectively.
It is concluded that CAPE is an effective proliferation inhibitor and radiosensitizer for Daoy cells. It has potential as an adjunct to the clinical adjunctive therapy for human medulloblastoma.
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