论文部分内容阅读
为了寻找更加有效的诱导分化剂，我们测试了两种新的维生素Ｄ＿３类似物（ＥＢ１０８９和ＭＣ９０３）对人早幼粒细胞白血病细胞系（ＨＬ－６０）和人巨核细胞白血病细胞系（ＨＩＭｅｇ－１）的体外抑制生长和诱导分化作用。集落形成试验结果显示ＥＢ１０８９，ＭＣ９０３和１，２５（ＯＨ）＿２Ｄ＿３抑制ＨＬ－６０细胞生长的ＥＤ＿（５０）分别为９×１０￣（－９）ｍｏｌ／Ｌ，１×１０￣（－８）ｍｏｌ／Ｌ和７×１０￣（－８）ｍｏｌ／Ｌ它们抑制ＨＩＭｅｇ－１细胞生长的ＥＤ＿（５０）则分别为７×１０￣（－１１）ｍｏｌ／Ｌ，４．５×１０￣（－１０）ｍｏｌ／Ｌ和１×１０￣（－８）ｍｏｌ／Ｌ。形态学检查、硝基四氮唑蓝反应以及细胞表面分化抗原检测表明三者均可促使白血病细胞向成熟单核细胞分化。ＥＢ１０８９诱导分化活性最强，ＭＣ９０３和１，２５（ＯＨ）＿２Ｄ＿３相近。流式细胞仪分析得知：经上述诱导剂作用后，Ｇ＿０／Ｇ＿１期细胞增加，Ｓ期细胞减少。点杂交结果表明：上述诱导剂可使ｃ－ｍｙｃ癌基因ｍＲＮＡ表达迅速下降。本研究结果提示：ＥＢ１０８９和ＭＣ９０３（特别是前者）对白血病细胞的逆转作用强于１，２５（ＯＨ）＿２Ｄ＿３，以往研究表明它们的毒性作用却低于?
In search of more potent inducer, we tested two novel vitamin D-3 analogs (EB1089 and MC903) against the human promyelocytic leukemia cell line (HL-60) and the human megakaryocytic leukemia cell line (HIMeg-1). ) inhibit growth and induce differentiation in vitro. The results of colony formation assay showed that the ED_(50) of EB1089, MC903 and 1,25(OH)_2D_3 inhibited the growth of HL-60 cells was 9×10 ̄ (-9) mol/L and 1×10 ̄ (-8) mol, respectively. The ED_(50) that inhibited the growth of HIMeg-1 cells was 7×10 ̄ (-11) mol/L and 4.5×10 ̄(-10), respectively. )mol/L and 1×10 ̄(-8) mol/L. Morphological examination, nitroblue tetrazolium reaction, and cell surface differentiation antigen detection showed that all three could promote the differentiation of leukemic cells into mature monocytes. EB1089 had the strongest differentiation-inducing activity, and MC903 was similar to 1,25(OH)_2D_3. Flow cytometry analysis showed that after the above-mentioned inducer, cells in G 0 /G 1 phase increased, and cells in S phase decreased. Dot hybridization results showed that the above inducer can rapidly decrease the expression of c-myc oncogene mRNA. The results of this study suggest that the reversal effect of EB1089 and MC903 (especially the former) on leukemia cells is stronger than that of 1,25(OH)_2D_3. Previous studies have shown that their toxicity is lower than that of EB1089 and MC903 (especially the former).