2-氯脱氧腺苷对多药耐药白血病细胞的毒性实验研究

Experimental study on cytotoxicity of 2-chlorodeoxyadenosine on multidrug-resistant leukemic cell

目的 探讨 2 -氯脱氧腺苷 (2 - CDA)对多药耐药白血病细胞 (K5 6 2 / A0 2 )的毒性作用。方法 细胞毒实验采用 MTT法 ,二药合用时细胞毒性作用采用 Chou- Talalay联合指数法分析。结果 2 - CDA对 K5 6 2和K5 6 2 / A0 2的 IC50 分别为 (2 3.9± 2 .4) nmol/ L 和 (137.6± 12 .7) nm ol/ L(P<0 .0 5 )。 2 - CDA与柔红霉素 (DNR)联合应用时 ,对 K5 6 2细胞的联合指数分别是 1.0 ,对 K5 6 2 / A0 2细胞为 5 .1。结论 2 - CDA对敏感白血病细胞具有明显细胞毒性作用。多药耐药白血病细胞对 2 - CDA不敏感。2 - CDA与 DNR联合应用时 ,对敏感白血病细胞的毒性为相加作用 ,对多药耐药白血病细胞的毒性为拮抗作用。

Objective To explore the cytotoxicity of 2-chlorodeoxyadenosine (2-CDA) to sensitive or multidrug-resistant (MDR) K562 leukemia cell line.Methods MTT assay was used to detect the cytotoxicity,the combined effect of two drugs was analyzed with Chou-Talalay combination index (CI).Flow cytometry was used to detect the P-glycoprotein (P-gp)on the surface of the cells and the intracellular daunorubicin (DNR).Results The IC 50 of 2-CDA to K562 and K562/A02 was (23.9±2.4)nmol/L and (137.6±12.7) nmol/L,respectively (P>0.05).The combination index (CI) of 2-CDA combined with DNR to K562 cell line was 1.0,and to the K562/A02 was 5.1.The fluorescence of P-glycoprotein on the surface or of the DNR inside cells detected was not significantly different before and after the K562/A02 cell line exposing to 2-CDA.Conclusion The toxicity of 2-CDA to K562 cell line is remarkable.The multidrug-resistant leukemic cells do not well respond to 2-CDA.The effect of 2-CDA combined with DNR shows synergism on K562 and antagonism on K562/A02 cell line.2-CDA does not influence the synthesis or the function of P-gp.