經動脈血管化學栓塞術對於手術未能切除之肝癌為一重要的治療方
法，而 daunorubicin 常合併使用於經肝動脈血管化學栓塞術。關於 daunorubicin
之作用機制，較早年的研究指出其與抑制 topoisomerase II 有關，近年來之研究
則多半與細胞凋亡或細胞週期之抑制有關，然其確定之機轉尚未完全明朗。
本 研 究 之 實 驗 結 果 顯 示 daunorubicin 在 Anchorage- independent
transformation assay 實驗中確能有效抑制肝細胞的轉形，且以 luciferae assay 分析 之結果發現 daunorubicin 可以抑制 Chang liver/AP-1 及 HepG2/AP-1 之 AP-1 活
性，細胞週期分析則顯示 daunorubicin 對於細胞週期之作用主要在 G2/M 期休
止。但相對於 daunorubicin 於 anchorage- independent transformation assay 及細胞
週期分析之顯著效果，daunorubicin 抑制 AP-1 的活性較不明顯，因此，AP-1 應
非 daunorubicin 抑制細胞轉形之主要途徑。
本研究之限制為細胞實驗模式，藥物之作用於活體內時，尚須考慮代謝
等生理因素。藥物對於細胞 AP-1 活性之影響外，尚須進一步探討 AP-1 組成成
分 Jun 及 Fos 及其磷酸化之影響，而 AP-1 所啟動的基因作用之標的對於細胞所
產生的影響如何。又 daunorubicin 對於細胞週期產生 G2/M 休止作用，卻也有研
究顯示是 G1/S 期，最主要影響因子可能是劑量及細胞模式，加上對於細胞凋亡
影響的程度，daunorubicin 對於細胞週期及細胞凋亡之影響值得做進一步更廣泛
的探討。
成，確為良好之抗肝腫瘤藥物，其作用於肝癌細胞株之主要作用為對於 G2/M 細
胞週期的抑制，對於其更詳細的分子機制值得進一步探討。
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圖一、Daunorubicin 對於腫瘤細胞轉形之抑制作用，與 activator protein-1 及細胞
週期之可能關係。
Daunorubicin
Tumor suppression
Cell cycle AP-1
Cell transformation
圖二、探討 daunorubicin 對於肝細胞株作用分子機轉之實驗架構。
Anchorage-independent transformation assay 探討 daunorubicin 是否可以抑制腫瘤
細胞之生長
探討藥物對於肝細胞作用之分子機制
以肝癌細胞株/AP-1 報導基因 探討 daunorubicin 是否可抑制
AP-1 之活性
細胞週期分析探討 daunorubicin 對於細胞週期之影響 是否造成細胞之重新分佈
藉由以上實驗結果探討 daunorubicin 對於腫瘤細胞作用之分子機制
0
Mitomysin CPaclitaxelVinblastineVincristine
Relative fold
圖三、各類藥物在 Anchorage- independent transformation assay 中對於 HepG2 細胞 之影響。將 HepG2 細胞株分別培養於含有各類藥物之 agar 中，經過 21 天之後，
在相位差顯微鏡下觀察細胞 colony 的型態，並以團塊總面積計數的方式來比較 各細胞受藥物影響之程度。結果為將 TPA 組面積為單位基準所得之相對倍率結 果。
0 50 100 150 200 250 300 350
mock
TPA20ng
T+DNR0.01uM T+DNR0.1uM T+DNR1uM T+DNR10uM
soft agar colonies/104 cells