本研究為了尋求有效之細胞分化劑，著者針對一系列苯醋酸類 緣物進行促使細胞分化作用與抑制細胞增殖作用之篩選工作。由實驗 結果發現化合物10-1與11-1單獨使用時，促使人類前骨髓性血癌細 胞之分化作用效果最顯著，而併用全反式維甲酸之後的分化效果也最 強；於是進一步地以細胞表面抗原表現與其對細胞週期之影響來探討 其初步作用機轉。 當10-1與11-1單獨使用時，10-1的實驗結果與全反式維甲酸 相似；會有細胞週期停留在G0 / G1期與分化走向顆粒球路徑的現象 出現。11-1的實驗結果只有細胞週期停留在G0 / G1期與全反式維甲 酸相似，而細胞分化會同時走向顆粒球路徑與單核球路徑。當10-1 與11-1併用全反式維甲酸時，其實驗結果都與全反式維甲酸相似； 細胞週期停留在G0 / G1期與分化走向顆粒球路徑。由以上結果推論： 化合物10-1與11-1單獨使用或併用全反式維甲酸都可望成為新一類 型之急性前骨髓性白血病治療藥物。; In order to develop the novel cell differentiation agents, a series of phenylacetic acid analogs was screened for their differentiation and anti-proliferation activities of HL-60 cells. Compounds 10-1 and 11-1 were found to be the most effective to differentiate and to be the most effective to potentate the induction of differentiation by all-trans retinoic acid (ATRA). Therefore the further studies were carried out to evaluate their effects on the cell cycle and cell surface antigen expression of HL-60 cells. When treatment of compounds 10-1 and 11-1alone, compound 10-1 was found to affect the cell cycle and cell surface antigen expression in the same manner as ATRA, which occurred G0 / G1 phase arrest and differentiated to granulocytic pathway; compound 11-1 was found to affect the cell cycle in the same manner as ATRA, but differentiated to granulocytic and monocytic pathway. When treatment combined with ATRA, compounds 10-1 and 11-1 were found to affect the cell cycle and cell surface antigen expression in the same manner as ATRA. This finding suggests that compounds 10-1 and 11-1 when administered alone or together with ATRA may have beneficial therapeutic effects in the treatment of acute promyelocytic leukemia (APL).
