(E)-2-(4-二乙基胺甲基-苯亚甲基)-5,6-二甲氧基-2,3-二氢-1-茚酮与P-糖蛋白的相互作用

Interaction between(E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one and P-glycoprotein

考察(E)-2-(4-二乙基胺甲基-苯亚甲基)-5,6-二甲氧基-2,3-二氢-1-茚酮(BYZX)在Bcap37和P-糖蛋白(P-gp)高表达的Bcap37/MDR1细胞中的积聚差异,以确证BYZX是否为P-gp的底物。同时,以罗丹明123为底物,比较在上述两种细胞中BYZX对罗丹明123积聚的影响,从而确证BYZX是否是P-gp的抑制剂。采用HPLC法测定BYZX在两种细胞中的累积量,酶标仪法测定细胞内罗丹明123的荧光强度。实验结果显示,BYZX在Bcap37及Bcap37/MDR1细胞内不同时间下的积聚量无明显差异(P>0.05),且不同浓度的BYZX对罗丹明123的外排亦无明显的抑制作用(P>0.05)。这一结果表明BYZX与P-gp没有明显的相互作用,不会被P-gp外排到细胞外而影响其吸收,同时BYZX对P-gp也不存在抑制作用。

Cell lines of Bcap37 and Bcap37/MDR1（the high P-glycoprotein（P-gp） expressing cell line） were used as model to investigate the different accumulations of（E）-2-（4-（diethylamino methyl） benzylidene）-5,6-dimethoxy-2,3-dihydroinden-one（BYZX） in the two kinds of cells.It was authen-ticated that whether BYZX was the substrate of P-gp.Meanwhile,the inhibitive effects of BYZX on the（P-gp） were investigated by determining the fluorescence intensity of rhodamine 123 in the model cells,with and without BYZX.A reversed-phase high-performance liquid chromatography（RP-HPLC） method was used to determine the accumulations of BYZX in the two cells.The results showed that the amount of BYZX accumulation in Bcap37/MDR1 cells were as many as those in Bcap37 cells（P〉0.05）,and the concentrations of BYZX accumulated in the Bcap37/MDR1 cells did not increase when co-incubated with P-gp inhibitor verapamil.Furthermore,different concentrations of BYZX also had no effects on the efflux of rhodamine 123（P〉0.05）.These results indicated that there were no interactions between BYZX and P-gp.BYZX will not be pumped out of the cells,and it also not inhibited the P-gp.It was the useful advantage for its absorption.