Ikezaki K, Black K L
Jonsson Cancer Center, Division of Neurosurgery, UCLA School of Medicine 90024.
Cancer Lett. 1990 Feb;49(2):115-20. doi: 10.1016/0304-3835(90)90146-o.
The effects of peripheral benzodiazepine receptor ligands on cell proliferation were evaluated. PK11195 increased the growth rate of C6 glioma cells by 20-30% in the nanomolar range in serum free medium. [3H]thymidine incorporation into C6 glioma cells also were increased 22% and 25% after treatment by PK11195 and Ro5-4864, respectively. The effect of PK11195 as a mitogenic agent was estimated by mitogenic agent was estimated by [3H]thymidine incorporation using Swiss 3T3 cells. PK11195 increased DNA synthesis 170% over control at 10 nM. Higher concentrations of benzodiazepines showed inhibition of the DNA synthesis. Peripheral benzodiazepine binding sites underwent downregulation after exposure to serum free medium or to 10 nM PK11195. These findings suggest that peripheral benzodiazepines may be involved in the regulation of cell proliferation as a growth factor in lower concentration and as a antiproliferative agent in higher concentration.
评估了外周苯二氮䓬受体配体对细胞增殖的影响。在无血清培养基中，PK11195在纳摩尔浓度范围内使C6胶质瘤细胞的生长速率提高了20% - 30%。用PK11195和Ro5 - 4864处理后，[³H]胸腺嘧啶核苷掺入C6胶质瘤细胞的量分别增加了22%和25%。使用瑞士3T3细胞，通过[³H]胸腺嘧啶核苷掺入来评估PK11195作为促有丝分裂剂的作用。在10 nM时，PK11195使DNA合成比对照增加了170%。更高浓度的苯二氮䓬显示出对DNA合成的抑制作用。暴露于无血清培养基或10 nM PK11195后，外周苯二氮䓬结合位点发生下调。这些发现表明，外周苯二氮䓬可能在低浓度时作为生长因子参与细胞增殖的调节，而在高浓度时作为抗增殖剂。
