摘要
目的：探讨几种有效的抗肿瘤药多药抗药性（ＭＤＲ）逆转剂对ＭＤＲ细胞膜脂流动性及Ｐ糖蛋白（Ｐｇｐ）表达的影响，以阐明其逆转ＭＤＲ机理。方法：细胞株为抗阿霉素人乳腺癌细胞ＭＣＦ７／ＡＤＲ及其相应的敏感株ＭＣＦ７。Ｐｇｐ表达测定采用Ｗｅｓｔｅｒｎｂｌｏｔ法，膜脂流动性的测定采用ＤＰＨ标记的荧光分光光度计法。结果：在无逆转剂存在时，ＭＣＦ７／ＡＤＲ细胞的荧光偏振度显著低于ＭＣＦ７细胞，吲哚衍生物２苯３（３’，５’双吗啉甲基４’羟基）苯甲酰吲哚（ＨＷＬ１２）及吗丙嗪（Ｐｒｏ）显著增加ＭＣＦ７／ＡＤＲ细胞的荧光偏振度，即降低膜脂流动性。苄普地尔（Ｂｅｐ）及维拉帕米（Ｖｅｒ）对ＭＣＦ７／ＡＤＲ细胞的荧光偏振度无影响，即不能改变膜脂流动性。Ｖｅｒ、Ｂｅｐ、ＨＷＬ１２能显著地降低Ｐｇｐ表达，而Ｐｒｏ无此作用。结论：ｐｒｏ逆转ＭＤＲ的作用可能与降低ＭＤＲ细胞膜脂流动性有关；Ｂｅｐ及Ｖｅｒ可能与降低Ｐｇｐ表达有关；ＨＷＬ１２可能既与降低ＭＤＲ细胞的膜脂流动性有关，也与降低Ｐｇｐ表达有关。
Objective:
To explore the possible reversal mechanism of multidrug resistance(MDR),the effects of
probimane(Pro),2phenyl3(3',5'dimorpholinomethyl4'hydroxy)benzoylindole (HWL-12),bepridil
(Bep) and verapamil (Ver)on Pglycoprotein(Pgp)expression and membrane fluidity in MCF7/ADR
and MCF7 cells were studied. Methods: Pgp expression was determined by western
blot.Membrane fluidity was determined by fluorescence spectrophotometry measurement with
DPH label. Results: The membrane fluidity was higher in MCF7/ADR than in MCF7HWL12 and
Pro could reduce the membrane fluidity in MCF7/ADR,while Bep and Ver could not.Ver,Bep and
HWL12 could decrease Pgp expression in MCF7/ADR, but Pro did not. Conclusion: The
decrease of membrane fluidity was associated with the reversal of MDR by pro. The decrease
of Pgp expression was associated with the reversal of MDR by ver and bep. The decreases of
both Pgp expression and membrane fluidity were involved in the reversal of MDR by HWL12.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
1999年第3期270-272,共3页
Chinese Journal of Cancer
基金
广东省科委自然科研基金
关键词
肿瘤细胞
多药耐药
逆转剂
P-糖蛋白
膜脂流动性
Multidrug resistance
Probimane
Bepridil
HWL12
Verapamil
Pglycoprotein
Membrane
fluidity
