苯丙素甙化合物逆转大肠癌LoVo/Adr细胞多药耐药性

Phenylpropanoid glycosides reversing effect on multidrug resistance of colon carcinoma LoVo/Adr cells

目的:以大肠癌LoVo/Adr耐药株为实验对象,观察苯丙素甙(PPG)化合物逆转多药耐药(MDR)作用及可能机制.方法:采用MTT法检测PPG对LoVo细胞和LoVo/Adr细胞增殖的影响.用PPG小于IC10(存活率>90%)的剂量进行耐药逆转试验,确定半数抑制浓度(IC50)并计算逆转倍数.流式细胞术检测PPG对LoVo/Adr细胞阿霉素(ADR)的摄入影响;荧光显微镜观察PPG对ADR在细胞中分布的影响.结果:当PPG浓度为80,160mg/L时,LoVo细胞存活率分别为(69.34±3.48)%,(30.15±1.86)%;LoVo/Adr细胞分别为(67.89±2.87)%,(34.96±2.14)%,提示PPG具有抑制细胞增殖作用且具有一定的量效关系(P<0.05).当PPG浓度小于40mg/L时,LoVo/Adr,LoVo细胞存活率均大于90%;PPG浓度为20,40mg/L时,逆转倍数分别为5.24,9.78.ADR主要分布在LoVo/Adr细胞胞质区,加用PPG后,胞质区荧光强度从2.04±0.70升至2.35±0.87,摄入能力显著增强(P<0.05).结论:PPG具有抗肿瘤、逆转耐药作用,PPG通过增加LoVo/Adr细胞对ADR的摄入及细胞胞质区积聚是其逆转耐药机制之一.

AIM：To investigate the effect of phenylpropanoid glycosides（PPG）on reversing multidrug resistance（MDR）of coloncarcinoma LoVo/Adr cells and its possible mechanism.METHODS：The effects of PPG on proliferation of LoVo and LoVo/Adr cells were examined by MTT.The reversing test of PPG on MDR was identified when its IC10 was10%;its IC50and reversal fold was subsequently calculated.Flow cytometry technique was applied to determine the influence of PPG on the uptake of adriamycin（ADR）.The subcellular distribution of ADR in the cells was observed by fluorescence microscopy.RESULTS：At a concentration of 80 and 160 mg/L of PPG,the survival rate of LoVo cells was（69.34±3.48）% and（30.15±1.86）%,respectively;while the survival rate of LoVo/Adr cells was（67.89±2.87）% and（34.96±2.14）%,respectively.Therefore,PPG significantly inhibited proliferation of cells in a dose-dependent manner（P〈0.05）.However,when the concentration of PPG was less than 40 mg/L,the survival rate of LoVo cells as well as LoVo/Adr cells was more than 90%.Reversal fold was 5.24 and 9.78 corresponding to a concentration of 20 and 40 mg/L of PPG,respectively.Reversal fold was also dose-dependent.The distribution of fluorescent ADR waspredominantly localized in the nucleus,and the intensity of ADR fluorescence was significantly increased from（2.04±0.70）to（2.35±0.87）（P〈0.05）,after treatment with PPG.CONCLUSION：PPG significantly inhibits carcinoma and reverses multidrug resistance of LoVo/Adr cells.By increasing the uptake of ADR and preferably accumulating ADR in nuclei of LoVo/Adr cells is probably one of mechanisms to explain the reversingeffect of PPG on MDR.