摘要
目的探讨与钾离子通道HERG相关的药物在肿瘤治疗中的靶向调节作用。方法采用Western blot检测相关蛋白的表达水平。采用MTT法观察SPFX-ERM对细胞增生的抑制作用;采用两药相互作用指数CDI评价是否存在协同作用。采用流式细胞术检测细胞周期。建立小鼠移植肝癌模型,观察连续灌胃给予SPFX-ERM的抑瘤效果。结果 HERG蛋白在人结肠癌细胞HCT116和HT-29中均高表达。MERG蛋白在小鼠肝癌H22细胞中也高表达。SPFX-ERM能明显抑制人结肠癌HCT116和HT-29细胞的增生,并且细胞对两药联合的敏感性要显著高于单用SPFX或ERM。高剂量的SPFX-ERM能抑制HERG蛋白的表达。SPFX-ERM可以引起G2期细胞阻滞。动物体内实验表明,SPFX-ERM能明显抑制小鼠移植性肝癌H22在体内的生长,协同作用显著,其CDI值均在0.7以下。结论联合SPFX-ERM作为与HERG有关的调节剂有显著的抗肿瘤作用。
Objective To study the targeted modulation of the drugs targeted ion channel-HERG.Methods The protein expression level was detected by Western blot.MTT assay was used to detect the cytotoxicity.Flow cytometry was used to analyze cell cycle distribution.Transplantable murine hepatoma 22 model was used to evaluate the antitumor activity of drugs in vivo.Results HERG and MERG proteins were over-expressed in human colorectal cancer cells and mouse hepatoma cells respectively.The colon cancer cells were more sensitive to the combination drugs SPFX-ERM than respective drug alone.The higher dose of the combined drugs showed inhibition on the expression of HERG.SPFX-ERM induced a dose-dependent increase in the fraction of cells in G2 phase of the cell cycle.The inhibition of tumor growth by SPFX-ERM was stronger than that by SPFX or ERM alone in transplantable hepatoma 22-bearing mice,and the synergistic effects were very significant with CDI0.7.Conclusion The combined antibacterial agents SPFX-ERM,as a modulator targeting HERG channel,is of in vitro and in vivo antitumor effect.
出处
《医学研究杂志》
2011年第1期54-59,共6页
Journal of Medical Research
基金
国家重点基础研究发展计划("973"计划)基金资助项目(2004CB518706)
