Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells.
Specific ligands of the peripheral benzodiazepine receptor induce apoptosis and cell cycle arrest in human colorectal cancer cells.
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外周苯二氮卓受体的特定配体诱导人结肠直肠癌细胞中的细胞凋亡和细胞周期停滞。
DOI：
10.1054/bjoc.2001.2181
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发表时间：
2001-11-30
影响因子：
8.8
通讯作者：
Scherubl, H
中科院分区：
文献类型：
--
作者：
Maaser, K;Hopfner, M;Jansen, A;Weisinger, G;Gavish, M;Kozikowski, A P;Weizman, A;Carayon, P;Riecken, E O;Zeitz, M;Scherubl, H
外周苯二氮卓类受体(PBR)参与了多种肿瘤模型的生长控制。虽然在结直肠癌中发现了PBR的过度表达，但到目前为止，PBR在结直肠癌生长中的功能作用还没有得到解决。利用原代培养的人结直肠癌细胞和人结直肠癌细胞系HT29、LS174T和Colo320 DM，我们研究了PBR在结直肠癌生长控制和细胞凋亡中的作用。逆转录-聚合酶链式反应和流式细胞仪检测PBR的mRNA和蛋白表达。用激光共聚焦扫描显微镜和免疫组织化学方法将PBR定位于线粒体。PBR特异性配体FGIN-1-27、PK 11195或Ro5-4864呈剂量依赖性抑制细胞增殖。FGIN-1-27降低线粒体膜电位，提示细胞凋亡的早期事件。此外，FGIN-1-27、PK 11195或Ro5-4864提高了caspase-3的活性。除了诱导细胞凋亡外，PBR配体还能诱导细胞周期停滞于G1/G0期。因此，我们的数据显示了PBR在结直肠癌生长中的功能参与，并使PBR有资格成为结直肠癌创新治疗方法的可能靶点。©2001癌症研究活动http://www.bjcancer.com
The peripheral benzodiazepine receptor (PBR) has been implicated in growth control of various tumour models. Although colorectal cancers were found to overexpress PBR, the functional role of PBR in colorectal cancer growth has not been addressed to date. Using primary cell cultures of human colorectal cancers and the human colorectal carcinoma cell lines HT29, LS174T, and Colo320 DM we studied the involvement of PBR in the growth control and apoptosis of colorectal cancers. Both mRNA and protein expression of PBR were detected by RT-PCR and flow cytometry. Using confocal laser scanning microscopy and immunohistochemistry the PBR was localized in the mitochondria. The specific PBR ligands FGIN-1-27, PK 11195, or Ro5-4864 inhibited cell proliferation dose-dependently. FGIN-1-27 decreased the mitochondrial membrane potential, which indicates an early event in apoptosis. Furthermore, FGIN-1-27, PK 11195 or Ro5-4864 increased caspase-3 activity. In addition to their apoptosis-inducing effects, PBR ligands induced cell cycle arrest in the G 1/G 0-phase. Thus, our data demonstrate a functional involvement of PBR in colorectal cancer growth and qualify the PBR as a possible target for innovative therapeutic approaches in colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com