出核因子CRM1抑制剂KPT-185对人前列腺癌细胞生长的影响

目的 探讨出核因子（chromosome maintenance region 1, CRM1）抑制剂KPT-185对人前列腺癌细胞生长、凋亡、迁徙的影响及影响产生的原因。方法 采用MTT、细胞集落形成能力测定法检测KPT-185对前列腺癌细胞生长的影响；划痕愈合实验检测KPT-185对前列腺癌细胞迁徙能力的影响；流式细胞仪检测KPT-185对细胞周期的影响；人组蛋白（Histone）/DNA 酶联免疫法和膜联蛋白V-FITC/PI双染法流式细胞术检测细胞凋亡；免疫印迹检测蛋白表达。结果 KPT-185能极大地抑制人前列腺癌细胞的生长，使其细胞周期阻滞于G0~G1期，并导致细胞凋亡。KPT-185引起的细胞生长抑制和凋亡是通过其抑制CRM1的核输出，使抑癌蛋白p53 和p21保留于核内而发挥作用的。结论 KPT-185是一种新型的CRM1抑制剂，有望成为治疗前列腺癌的候选药物。

Effect of CRM1 Inhibitor KPT-185 on Growth of Human Prostate Cancer Cells

Objective To investigate the effect of chromosome maintenance region 1(CRM1) inhibitor KPT-185 on the growth, migration and apoptosis of prostate cancer cells and related reasons.Methods MTT assay, Clonogenic assay, Wound healing assay, flow cytometry analysis, Histone/DNA ELISA, Annexin V-FITC method and Western blot were used to detect KPT-185 effect on cell growth, migration, cell cycle, apoptosis, protein expression in prostate cancer cells and the potential mechanism, respectively. Results KPT-185 induction of cell apoptosis, growth inhibition and cell cycle arrest was involved in CRM1 inhibition and nuclear retention of tumor suppressor proteins p53 and p21 in prostate cancer cells. Conclusion KPT-185 as a new CRM1 inhibitor could be a potential drug in the treatment for prostate cancer.