双苄基异喹啉类生物碱粉防己碱与小檗胺逆转多药抗药性的比较研究

A COMPARATIVE STUDY ON EFFECT OF TWO BISBENZYLISOQUINOLINES,TETRANDRINE AND BERBAMINE, ON REVERSAL OF MULTIDRUG RESISTANCE

比较了２种结构相近的双苄基异喹啉（ＢＢＩ）生物碱粉防己碱（ＴＴＤ）、小檗胺（ＢＢＭ）与维拉帕米（ＶＲＰ）逆转多药抗药性的作用。结果，ＴＴＤ，ＢＢＭ和ＶＲＰ在多药抗药的ＭＣＦ７／Ａｄｒ和ＫＢｖ２００细胞对ＡＤＲ和ＶＣＲ均有明显增敏作用，且作用呈剂量依赖性。其中１０μｍｏｌ·Ｌ－１ＴＴＤ能完全逆转ＭＣＦ７／Ａｄｒ细胞对ＡＤＲ的抗药性。ＴＴＤ，ＢＢＭ和ＶＲＰ均有增加ＭＣＦ７／Ａｄｒ细胞内阿霉素积累的作用。ＴＴＤ和ＢＢＭ在结构上仅有微小差别，但ＴＴＤ的逆转ＭＤＲ作用优于ＶＲＰ１０倍，而ＢＢＭ的作用与ＶＲＰ相仿。ＴＴＤ在裸鼠体内ＭＣＦ７／Ａｄｒ实体瘤模型上也证实有明显逆转ＡＤＲ抗药性的作用。

A comparative study on the effect of two bisbenzylisoquinolines, tetrandrine (TTD) and berbamine (BBM), and verapamil (VRP) on reversing multidrug resistance was reported. TTD, BBM and VRP showed significant activity in reversing adriamycin (ADR) and vincristine (VCR) resistance in acquired resistant MCF 7/Adr and KBv 200 cell lines, and the effect was shown to be dose dependent. TTD, at the concentration of 10 μmol·L -1 , completely reversed ADR resistance in MCF 7/adr cells. TTD, BBM and VRP increased intracellular ADR accumulation in MCF 7/Adr cells. There is minor difference in structure between TTD and BBM. TTD showed greater activity than VRP in reversing MDR, while BBM showed similar activity to that of VRP. TTD also showed significant activity in vivo in reversing ADR resistance in MDR MCF 7/Adr solid tumor in nude mice.