人工合成钠离子通道阻断剂抑制乳腺癌细胞生长的研究

Evaluation of anticancer efficacy of novel synthetic sodium channel blockers in breast cancer cell lines

目的探讨人工合成钠离子通道阻断剂-钠离子胺类配体(sodium channel amine ligands,SCALs)对乳腺癌细胞株(MCF-7、MDA-MB-231)的抑制效果,以筛选高效的抗肿瘤药物。方法在药物作用后,采用MTT法检测肿瘤细胞的增殖活性;流式细胞术检测SCALs促进细胞凋亡及阻滞细胞周期的能力。结果 7种SCALs中的S1127对乳腺癌细胞敏感,肿瘤细胞增殖明显受到抑制,且其抑制率与药物浓度呈剂量-效应关系,S1127对MCF-7细胞和MDA-MB-231细胞的IC_(50)分别为17.2μM和21.8μM,在25μM时能促进80.6%的MCF-7细胞凋亡以及18.4%的MDA-MB-231细胞凋亡,并将细胞阻滞于G0/G1期。结论合成的钠离子通道阻断剂S1127具有显著杀伤乳腺癌细胞效应,将来有可能成为治疗肿瘤的一类新型备选药物。

Objective To investigate the anticancer efifcacy of sodium channel blocker-sodium channel amine ligands (SCALs) in breast cancer cell lines.Methods Seven SCALs compounds, S1127, S1156, S1169, S1170, S1178, S1180, and S1182 were synthesized and structure conifrmed. Breast cancer cell lines, MCF-7 cell line and MDA-MB-231 cell line were used in this study. The cell viability was assessed by MTT Assay. The cell apoptosis and cell cycle progression were assessed by flow cytometry. Results S1127 was found to be the most potent among the seven compounds; it inhibited the growth of tumor cells in the low micro-molar range with a dose-dependent manner. The IC50 of S1127 is 17.2 μM and 21.8 μM for MCF-7 cells and MNA-MB-231 cells, separately. Further study on S1127 showed that it induced apoptosis and G0/G1 phase cell cycle arrest in MCF-7 cell line and MDA-MB-231cell line.Conclusions These results indicate that S1127 is a potential therapeutic agent for breast cancer.