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-18...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。展开更多
Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM...Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.展开更多
文摘目的探讨出核因子(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。
基金supported in part by grants from Fujian Provincial Department of Science & Technology(2009-CXB-57/ 2011J01252)Bureau of Science & Technology of Xiamen,China (3502Z20094012)
文摘Mantle cell lymphoma （MCL） is an aggressive histotype of B-cell non-Hodgkin lymphoma. The disease has no known cure, which prompts the urgent need for novel therapeutic agents. Chromosomal region maintenance 1 （CRM1） may play a role in human neoplasia and serve as a novel target of cancer treatment. This study summarizes MCL pathogenesis and determines the involvement of CRM1 in the regulation of several vital signaling pathways contributing to MCL pathogenesis, including the pathways of cell cycle progression, DNA damage response, phosphoinositide kinase-3, nuclear factor-kB activation, and chromosomal stability. A preclinical study is also presented to compare the CRNI1 status in MCL cell lines and primary MCL cells with normal B cells, as well as the therapeutic efficiency of CRM1 inhibition in MCL in vitro and in vivo, which make these agents potential targets of novel MCL treatments.
