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目的研究反义寡核苷酸对化疗药物阿霉素（ＡＤＭ）、足叶乙甙（ＶＰ－１６）及阿糖胞苷（Ａｒａ－Ｃ）体外抑制Ｋ５６２细胞克隆形成的影响，并探讨其可能的作用机制。方法体外甲基纤维素半固体培养观察各处理组Ｋ５６２细胞的克隆形成，流式细胞仪评价细胞的凋亡状况。结果实验浓度下单独应用ＡＤＭ、ＶＰ－１６或Ａｒａ－Ｃ，Ｋ５６２细胞集落存活率分别为４１．４１％、５０．２８％及５２．０８％，先用反义寡核苷酸ＡＳ－ｂ３ａ２处理，再用上述３种化疗药物，集落存活率则分别为１５．２０％、１９．７７％及２１．３２％（Ｐ＜０．０１）；单独应用ＡＳ－ｂ３ａ２，Ｋ５６２集落存活率为３９．３１％，流式细胞仪检测到ＡＳ－ｂ３ａ２处理后的Ｋ５６２凋亡细胞比例为２７．２％，联用ＡＤＭ后凋亡细胞比例为４６．２０％，而未处理组仅为７．４％。结论实验结果提示，反义ＢＣＲ－ＡＢＬ寡核苷酸ＡＳ－ｂ３ａ２能增强化疗药物ＡＤＭ、ＶＰ－１６或Ａｒａ－Ｃ对Ｋ５６２细胞克隆形成的抑制作用，其作用可能在于增强化疗药物体外诱导Ｋ５６２细胞的凋亡。
Objective To study the effect of antisense oligodeoxynucleotides on the inhibition of clonal formation of K562 cells by chemotherapeutic drugs adriamycin (ADM), etoposide (VP-16) and cytarabine (Ara-C) in vitro. The mechanism of action. Methods The proliferation of K562 cells in each treatment group was observed by semi-solid culture of methylcellulose in vitro, and the cell apoptosis was evaluated by flow cytometry. Results The colony survival rate of K562 cells was 41.41%, 50.28%, and 52.08%, respectively, when ADM, VP-16, or Ara-C were used alone at the experimental concentrations. The antisense oligonucleotide AS-b3a2 was used for the first treatment. With the above three kinds of chemotherapy drugs, the colony survival rates were 15.20%, 19.77%, and 21.32%, respectively (P<0.01). With AS-b3a2 alone, the colony survival rate of K562 was 39. At 31%, the proportion of apoptotic K562 cells treated with AS-b3a2 was 27.2% by flow cytometry, and the proportion of apoptotic cells after combined ADM was 46.20% compared with 7.4% for the untreated group. . Conclusion The experimental results suggest that antisense BCR-ABL oligonucleotide AS-b3a2 can enhance the inhibitory effect of chemotherapeutic agents ADM, VP-16 or Ara-C on the colony formation of K562 cells, which may be due to enhanced chemotherapeutic agents inducing K562 cells in vitro. Apoptosis.