延胡索乙素逆转多药耐药性人乳腺癌细胞MCF-7

Reversal effect of tetrahydropalmatine on multidrug resistance of human breast cancer cells MCF-7

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.