索拉非尼在HepG2与LO2细胞的摄取动力学

Uptake kinetics of sorafenib in HepG2 and LO2 cells

目的探讨索拉非尼在肝癌细胞(HepG2)与正常肝细胞(LO2)的摄取动力学特性。方法取正常培养的处于对数期的HepG2与LO2细胞株,加入含索拉非尼系列浓度的培养液,孵育后处理细胞,检测索拉非尼及细胞蛋白浓度,分析摄取动力学参数。结果HepG2与LO2细胞对索拉非尼的摄取随着浓度的增加而趋于饱和,但与LO2细胞相比较,HepG2细胞对索拉非尼的摄取量明显增加。当加入10 mol·L^(-1)的索拉非尼,HepG2与LO2细胞对索拉非尼的摄取随着时间的增加而增加,均在20 min时趋于饱和。HepG2细胞的摄取动力参数V_(max)为(684.14±78.19)pmol·mg protein^(-1)·min^(-1),K_(m)为(93.3±17.56)μmol·L^(-1);LO2细胞的摄取动力参数V_(max)为(335.61±69.73)pmol·mg protein^(-1)·min^(-1),K_(m)为(135.68±29.34)μmol·L^(-1);结果显示HepG2细胞对索拉非尼的摄取速率明显高于LO2细胞。结论索拉非尼在肝癌细胞中摄取量及摄取速率明显高于正常肝细胞,对肝癌细胞具有一定的靶向性。

Objective To determine the uptake kinetics of sorafenib in hepatoma cells(HepG2 cells)and normal hepatocytes cells(LO2 cells).Methods HepG2 and LO2 cell lines in logarithmic phase were incubated in the medium at various sorafenib concentrations.Sorafenib and cell protein concentrations were measured,and the kinetic parameters of sorafenib uptake were analyzed.Results The uptake of sorafenib in HepG2 and LO2 cells saturated with the concentration increase,but the sorafenib uptake in HepG2 cells was much higher than that in LO2 cells.After adding 10 mol·L^(-1),the sorafenib uptake in HepG2 and LO2 cells increased with time,and gradually reached saturation at 20 min.The uptake kinetic parameter V_(max) of HepG2 cell was(684.14±78.19)pmol·mgprotein^(-1)·min^(-1),and K_(m) was(93.3±17.56)μmol·L^(-1).The uptake kinetic parameter V_(max) of LO2 cell was(335.61±69.73)pmol·mg protein^(-1)·min^(-1),and K_(m) was(135.68±29.34)μmol·L^(-1).The uptake rate of sorafenib in HepG2 cells was obviously higher than that in LO2 cells.Conclusion Sorafenib uptake and uptake rate in the hepatoma cells are significantly higher than those in normal hepatocytes cells.Sorafenib has a certain targeting effect on the hepatoma cells.