蝙蝠葛酚性碱诱导多药耐药细胞系K562/MDR1凋亡及逆转耐药性的研究

Effects of phenolic alkaloids from Menispermum dauricum on inducing the multidrug resistance cell line K562/MDR1 to apoptosis and reversing their multidrug resistance

目的:探讨蝙蝠葛酚性碱(phenolic alkaloids from Menispermum dauricum,PAMD)诱导多药耐药(multidrug resistance,MDR)细胞系K562/MDR1凋亡及逆转耐药性的作用。方法:四甲基偶氮唑蓝(MTT)比色法检测K562/S及K562/MDR1细胞对不同浓度PAMD的敏感性,并计算半数抑制浓度(IC50)。膜联蛋白V(AnnexinV)-异硫氰酸荧光素(FITC)+碘化丙啶(PI)双参数检测细胞凋亡百分率变化,分析在PAMD的作用下,两种细胞对伊马替尼(IM,STI571)敏感性的变化。结果:PAMD可诱导两种细胞凋亡,其低剂量72h时对K562/S和K562/MDR1细胞的凋亡率分别为(10.92±1.03)%和(8.12±0.98)%,并可提高伊马替尼对K562/MDR1的凋亡率。PAMD可显著逆转K562/MDR1细胞对伊马替尼的耐药性,其逆转倍数为2.22。结论:PAMD对K562/S和K562/MDR1细胞具有诱导凋亡作用,同时具有逆转白血病细胞株K562/MDR1多药耐药性、回归靶位的作用。

Objective： To study the effects of phenolic alkaloids from Menispermum dauricum （PAMD） on inducing the multidrug resistance （MDR） cell line K562/MDR1 to apoptosis and reversing their MDR. Methods： MTr colorimetric assay was employed to detect the sensitivity of K562/S and K562/MDR1 cell lines treated with PAMD of different concentration for 72 h. ICs0 values of PAMD were analyzed by MTT assay. The apoptosis rates of the two cell lines were detected by Annexin V/PI to analyze the sensitivity of two cell lines treated with PAMD on imatimib mesylate （IM, STI571 ）. Results： PAMD can induce the apoptosis of the two kinds of cells and the apoptosis rates of the two cell lines were （ 10. 92 ± 1.03 ） % and （8. 12 ± 0. 98）% respectively. It was also able to enhance the apoptosis rates of K562/MDR1 on IM. PAMD could reverse MDR of K562/MDR1 on IM and its reversal multiple was 2.22. Conclusion： PAMD could induce K562/S and K562/MDR1 to apoptosis and reverse MDR of K562/MDR1 on IM and recur its target.