摘要
目的探讨延胡索乙素(Tetrahydropalmatine,Tet)逆转人乳腺癌细胞MCF-7多药耐药的作用机制。方法采用SRB法测定药物对细胞的毒性作用;通过免疫细胞化学技术分析药物对细胞Pgp、Lrp、Mrp、Gst、TopoⅡ等多药耐药相关蛋白表达的影响。结果Tet在浓度小于2.5μg/ml时对MCF-7无毒性作用,2.5μg/ml的Tet可明显逆转MCF-7/ADM耐药细胞的耐药性。MCF-7/S细胞不表达Pgp,而高表达TopoⅡ;MCF-7/ADM细胞Pgp高表达,但TopoⅡ低表达。Lrp、Mrp、Gst在MCF-7/S及MCF-7/ADM中的表达无明显差异。加入Tet后MCF-7/ADM细胞Pgp蛋白的表达明显下降,Topo的表达显著升高,其它几种蛋白的表达无明显变化。结论Tet具有逆转MCF-7细胞MDR的作用,主要通过下调肿瘤细胞内Pgp的表达、上调TopoⅡ的表达而达到逆转耐药的效果。
Objective: To investigate the reversal effect and mechanism of tetrahydropalmatine(Tet) against multidrug resistance (MDR) of human breast cancer cells MCF-7. Methods: The cytotoxic effect of chemothetherapeutic agents on MCF-7 cells was determined by SRB assay. The expression of Pgp, Lrp, Mrp, Gst and Topo Ⅱ in MCF-7 cells was examined by immunocytochemistry method. Results : Tet was nontoxic to MCF-7 cells when its concentration was less than 2.5μg/ml. However it obviously reversed the multidrug resistance of MCF-7/ADM. Topo Ⅱ was highly expressed while no expression of Pgp in MCF-7/S. In MCF-7/ADM, the expression of Pgp was increased, but Topo Ⅱ was less than in MCF-7/ADM. Meanwhile there was no significant difference of the expression of Lrp,Mrp,Gst between MCF-7/S and MCF-7/ADM ceils. Tet could decrease the expression of Pgp and increase the expression of Topo. But there was no effect on the expression of other proteins. Conclusions: Tet reversed the multidrug resistance of tumor cells by the way of decreasing the expression of Pgp and increasing the expression of Topo Ⅱ.
出处
《中药药理与临床》
CAS
CSCD
北大核心
2005年第6期19-21,共3页
Pharmacology and Clinics of Chinese Materia Medica
基金
江苏省中药局项目(095)