汉防己碱对白血病K562细胞生长的促进耐药作用

目的考察汉防己碱(Tet)对白血病K562细胞生长的影响。方法采用体外细胞培养,即在37℃、5%CO2、饱和湿度的培养箱中培养,培养液为含10%热灭活NBS的完全RPMI1640细胞培养基。待K562细胞与药物作用48 h后,收集并处理细胞,结合MTT和Western blot法研究Tet对K562细胞生长的作用特点。结果 Tet在0.33～1.00μg/ml仅使K562及K562/ADM细胞的存活率降低至75%～80%,低浓度Tet(0.33μg/ml)使阿霉素(ADM)和顺铂(cDDP)对K562细胞生长的IC50增加(P<0.01),1.0μg/ml Tet则降低IC50,使ADM对K562/ADM细胞的IC50增加,cDDP的IC50无明显变化。0.33μg/ml Tet有提升2种细胞的P-gp和MRP1表达的作用(P<0.05)。Tet各浓度对LRP表达无明显影响。结论 Tet对K562及K562/ADM细胞生长抑制作用具浓度依耐性,低浓度具加速耐药的作用,其促进耐药细胞发展的机制至少与提升P-gp和MRP1表达有关。

Promotion effect of tetrandrine on multidrug resistance in human leukemia K562 and K562/ADM cells

Objective To determine the effect of tetrandrine(Tet) on the growth of human leukemia K562 and K562/ADM cells.Methods The K562 and K562/ADM cells were cultured in RPMI1640 containing 10% newborn bovine serum(NBS) under the condition of 37 ℃ and 5% CO2.MTT assay and Western blot analysis were used to investigate the effect of Tet on the growth of K562 and K562/ADM cells after the cells were treated with Tet for 48 h.Results Tet(0.33-1.0 μg/ml) decreased the survival of K562 and K562/ADM cells to 75%-80%.The low dose of Tet(0.33 μg/ml) significantly increased the IC50 of doxorubicin(ADM) on K562/ADM cells and the IC50 of cisplatin(cDDP) on K562 cells(P<0.01),whereas the 1.0 μg/ml of Tet reduced the IC50 of cDDP on K562 cells(P<0.01).The IC50 of cDDP on K562/ADM cells was not affected.The expression of P-gp and multidrug resistance-related protein 1(MRP1) was significantly increased by 0.33 μg/ml of Tet in K562 and K562/ADM cells(P<0.05).The expression of lung resistance-related protein(LRP) in K562 and K562/ADM cells was not affected by varied concentrations of Tet.Conclusion The growth inhibition of K562 and K562/ADM cells by Tet is in a dose-dependent manner.Low dose Tet(0.33 μg/ml) promotes the drug resistance of K562 and K562/AMD cells to doxorubicin and cisplatin,and the mechanism is related to the upregulation of P-gp and MRP1.