TNFα诱导K562/VCR和K562细胞凋亡及逆转其耐药作用的实验研究  

Tumor necrosis factor alpha induces apoptosis of K562/VCR and K562 cells and reverses multidrug resistance

作　　者：庄静丽[1] 徐建民[1] 王宝珍[1] 吴直江[2] 高奇蓉[2] 

机构地区：[1]复旦大学附属中山医院血液科,上海200032 [2]中国医科院上海生化细胞所,上海200031

出　　处：《实用肿瘤杂志》2004年第4期296-300,共5页Journal of Practical Oncology

摘　　要：目的　探讨肿瘤坏死因子 α(TNFα)体外诱导 K5 6 2 / VCR及 K5 6 2细胞凋亡 ,及其逆转 K5 6 2 / VCR细胞多药耐药 (MDR)的作用机制。方法　以光镜、电镜、流式细胞仪观察细胞凋亡 ;流式细胞仪检测 P- gp和 bcl- 2表达。MTT检测药物敏感性。结果　 (1) TNFα浓度 >10 0 U/ m l,作用时间 >4 8小时 ,2株细胞均可见典型凋亡现象 ,以 K5 6 2 / VCR细胞明显。 (2 )以 TNFα10 0 0 U/ ml处理后 ,K5 6 2 / VCR和 K5 6 2细胞凋亡率分别为 2 9.4 %和10 .7%。 (3) K5 6 2 / VCR经 TNFα10 0 0 U/ ml处理 72小时 P- gp表达率从 93.6 %降至 82 .4 % ,bcl- 2表达率从32 .9%降至 7.0 %。 (4 ) K5 6 2 / VCR和 K5 6 2细胞分别经 TNFα10 0 U/ ml和 10 0 0 U/ ml处理后 ,VCR、Ara- C和VP- 16的药物敏感性增加 (P<0 .0 5 )。结论　 (1) TNFα可诱导 K5 6 2 / VCR和 K5 6 2细胞凋亡 ,以前者更加敏感 ,且存在时间和剂量依赖性。 (2 )高浓度 TNFα可下调 bcl- 2表达 ,但不显著改变 P- gp表达。 (3) TNFα能增加 K5 6 2 /VCR和 K5 6 2细胞对 VCR、Ara- C和 VP- 16的药物敏感性 ,以 K5 6 2 / VCR细胞更明显。 (4 ) TNFα逆转 K5 6 2 / VCR多药耐药是通过诱导细胞凋亡 ,降低 bcl- 2表达 ,而非下调 P-Objective To study the mechanism of apoptosis and reverse of multidrug resistance induced by tumor necrosis factor alpha(TNFα) in K562/VCR and K562 cells in vitro.Methods Apoptosis was observed by optic and electron microscopes and flow cytometry.P-gp and bcl-2 expression was assayed by flow cytometry.Drug chemosensitivity was analyzed by MTT.Results Apoptosis was more significant in K562/VCR cells than in K562 cells after exposured to 100 U/ml TNFα for 48 hours.After treatment with 1 000 U/ml TNFα,apoptosis rates of K562/VCR and K562 cells were 29.4% and 10.7%,respectively.After treatment with 1 000 U/ml TNFα for 72 hours,expression of P-gp decreased from 93.6% to 82.4%,and expression of bcl-2 from 32.9% to 7.0%.After treatment with TNFα,chemosensitivities of K562/VCR and K562 cells to VCR,Ara-C and VP-16 were increased (P<0.05).Conclusion TNFα can induce apoptosis both for K562 and K562/VCR cells;the mechanisum for TNFα to reverse MDR of K562/VCR may involve the downregulation of bcl-2 expression.

关 键 词：肿瘤坏死因子 K562细胞/药物学 P-糖蛋白 抗药性 多药 肿瘤细胞 培养的 流式细胞术 脱噬作用 

分 类 号：R733.7[医药卫生—肿瘤]