鲎素抑制多药耐药细胞HL-60/VCR生长的研究

Tachyplesin inhibited the growth of multidrug-resistant cell line HL-60/VCR

目的:探讨鲎血细胞来源的多肽鲎素是否能够抑制白血病多药耐药细胞HL-60/VCR细胞的生长。方法:HL-60细胞采用持续低浓度和逐渐增加长春新碱(VCR)浓度间歇诱导,建立多药耐药细胞HL-60/VCR;MTT法检测细胞耐药性及鲎素对HL-60/VCR细胞和HL-60细胞生长的影响;流式细胞仪检测HL-60/VCR细胞P-糖蛋白(P-glycoprotein,P-gp)和多药耐药相关蛋白(multidrug resistance-associated protein,MRP)的表达水平。结果:HL-60/VCR细胞对多种化疗药物产生耐药;HL-60/VCR细胞表面P-gp、MRP表达上调,分别为78.3%和58.3%(P<0.01)。鲎素无论对HL-60/VCR细胞还是对HL-60细胞均有抑制作用,作用呈剂量依赖性。HL-60/VCR细胞和HL-60细胞对鲎素具有相似的敏感性。鲎素能增强HL-60/VCR细胞对VCR的敏感性,但不影响HL-60/VCR细胞表达P-gp和MRP。结论:鲎素具有抗HL-60/VCR细胞耐药性并增加其对VCR敏感性的作用。

Objective：To investigate whether tachyplesin, a kind of peptide isolated from the hemocytes of horseshoe crabs, can inhibit the growth of multidrug-resistant leukemia cell line HL-60/VCR. Methods： Through continuous exposures to low-concentration of vincristine （VCR） and intermittant exposures to gradually increased-concentrations of VCR, HL-60 cells were induced to form multidrug-resistant cell line HL-60/VCR. The resistance of HL-60/VCR cells to chemotherapeutic agents and the effect of tachyplesin on the growth of HL-60/VCR cells were evaluated by MTT assay. The expressions of P-glycoprotein （P-gp） and multidrug resistance-associated protein （MRP） in HL-60/VCR cells were detected by flow cytometry. Results： HL-60/VCR cells had multidrug resistance to chemotherapeutic agents. The expressions of P-gp and MRP were up-regulated by 78.3% and 58.3% , respectively （ P 〈 0.01 ）. Tachyplesin inhibited the growth of HL-60/VCR and HL-60 cells in a dose-dependent manner. HL-60/VCR cells had similar sensitivity to tachyplesin with HL-60 cells. Tachyplesin enhanced the sensitivity of HL-60/VCR cells to VCR but had no effects on the expressions of P-gp and MRP. Conelusion：Tachyplesin reverses multidrug resistance of HL-60/VCR cells and enhances its sensitivity to VCR.