耐长春新碱KB细胞多药耐药性的新机理

New Mechanism of Multidrug Resistance to Vinblanstine in KB Cells

目的 :进一步研究肿瘤细胞多药耐药的机理。方法 :测定KB细胞及其耐药株的蛋白激酶C活性及细胞内游离Ca2 + 浓度。结果 :耐药株对长春新碱等的耐药性是亲本株KB细胞的 12～ 172倍 ,并表达耐药膜糖蛋白对罗丹明 12 3的蓄积减少、外排加速。耐药株细胞膜的蛋白激酶C的活性为 (6 8.32± 5 .6 0 ) pmol/min·mg-1,游离Ca2 + 浓度为 (2 5 3.6 3± 4 .37)nmol/L ;亲本株的分别为 (2 0 .75± 2 .0 0 )pmol/min·mg-1和 (14 5 .5 7± 1.0 0 )nmol/L ,耐药株的蛋白激酶C活性和Ca2 + 浓度均明显增高 (P <0 .0 1)。结论 :耐药性KB细胞的多药耐药性可能与其蛋白激酶C活性及细胞内游离Ca2 +

Objective: Our aim was to study the mechanism of multidrug resistance in cancer cells. Methods: We measured and compared the activity of protein kinase C and intracellular concentration of calcium ion in KB cells and vinblanstine-resistance KB cells(KB/VCR).Results: The resistance to vinblanstine was 12 to 172-fold higher in KB/VCR than that in KB cells. The expressions of P-glycoprotein were 47.5% and 5.8% respectively in KB/VCR and KB cells. The accumulation and efflux of Rhodamine 123 was decreased and accelerated respectively in KB/VCR.The activity of protein kinase C in cell membrane were (68.32±5.60) pmol/min·mg -1 in KB/VCR and (20.75±2.00) pmol/min·mg -1 in KB cells. The concentration of calcium ion was (253.63±4.37)nmol/L in KB/VCR and (145.57±1.00) nmol/L in KB cells. Conclusion: Resistance of KB/VCR is related to the activity of protein kinase C and intracellular concentration of calcium ion.