急性前骨髓性白血病( Acute Promyelocytic Leukemia , APL)的治療，利用全反式維甲酸( All-trans Retinoid Acid,ATRA)可以使急性前骨髓性白血病細胞走向分化( differentiation) ，臨床上可以使全部緩解率( complete remission rate)達到85-90%。但因為大多數的病人會有抗藥性的產生，所以無法維持長期的無疾病的緩解期( disease free remission)。而人尿萃取物(CDA-2)同樣也具有誘導急性前骨髓性白血病細胞走向分化的功能。本研究則希望合併使用CDA-2能加強ATRA在人類血癌細胞( HL-60)生長抑制作用。並利用Trypan Blue Exclusion方法、NBT還原方法( Nitroblue Tetrazolium reduction test)以及流式細胞分析儀中sub-G1期比率來探討其機轉。 CDA-2合併ATRA對 HL-60生長抑制的表現為加成(additive)的作用，合併使用CDA-2可以減少ATRA毒殺癌細胞所需的劑量。但因為CDA-2對ATRA誘導HL-60細胞凋亡上沒有加強的作用，所以在HL-60細胞生長抑制的表現上就沒有呈現協同( synergistic)的作用。此外，CDA-2對HL-60細胞誘導分化的表現與全反式維甲酸有協同的作用。如此便可以應用在急性前骨髓性白血病細胞病的治療，CDA-2增加誘導分化的療效，減少抗藥性的產生。 維他命C被認為會誘導HL-60細胞走向凋亡( apoptosis)， CDA-2同樣也具有誘導HL-60細胞凋亡的功能。本研究則希望合併使用CDA-2能加強維他命C在HL-60細胞生長抑制作用。並利用上述方法(同ATRA)探討其機轉。 而CDA-2合併維他命C 對HL-60細胞生長抑制的表現為協同的作用。合併使用CDA-2不但可以減少維他命C毒殺癌細胞所需的劑量，而且CDA-2對維他命C誘導HL-60細胞凋亡上呈現協同加強的作用。但對誘導分化的表現卻沒有顯著的加強作用。也就是在臨床上使用維他命C細胞毒殺及誘導凋亡作用於癌症的治療上，合併使用CDA-2是有協同的效果。更進一步可以考慮合併使用於化學治療上。; In the treatment of acute promyelocytic leukemia( APL), All-trans Retinoid Acid( ATRA) may induce APL cells into differentiation of APL.Although it has a clinically complete remission rate of 85-90% ,a longer remission period free of disease cannot maintained.CDA-2 may also induce APL cells into differentiation.In this study , we investigate the growth inhibition effect of ARTA in combination with CDA-2.We also seek to understand the mechanism via Trypan Blue Exclusion test,NBT reduction test and through the proportion of the sub-G1 phase in the flowcytometry. CDA-2 potentially inhibits the growth inhibition of ATRA throgh an additive effect.At the same,it can lower the ATRA’s cytotoxicity.However,CDA-2 dose not address the apoptosis effect in growth inhibition is present in HL-60 cells.Besides,CDA-2 address the differentiation of ATRA through synergistic effect.So in the treatment of APL,CDA-2 may increse the therapeutic efficacy and reduce the drug resistance associate with ATRA . Vitamin C is known to induce apoptosis in HL-60 cells CDA-2 may also induce HL-60 cells into apoptosis effct. In this study,we also look into the growth inhibition properties of Vitamin C in combination with CDA-2.Together,they lower the cytoxicity and synergistically inhibit growth in HL-60 cells.CDA-2 is able to increase apoptosis.But no difference was found with regards to differentiation.Thus, CDA-2 can synergistically increase the cytotoxicity and apoptosis associated with Vitamin C in the treatment of cancer.Therefore,chemotherapy in combination with CDA-2 may be better than chemotherapy alone.
