Hamilton H B, Hinton D R, Law R E, Gopalakrishna R, Su Y Z, Chen Z H, Weiss M H, Couldwell W T
Department of Neurosurgery, University of Southern California School of Medicine, Los Angeles, USA.
J Neurosurg. 1996 Aug;85(2):329-34. doi: 10.3171/jns.1996.85.2.0329.
Protein kinase C (PKC) is an enzyme involved in the regulation of cellular growth, proliferation, and differentiation in a number of tissues including the anterior pituitary, in which it is also believed to play a role in hormone secretion. Protein kinase C activity and expression have been found to be greater in adenomatous pituitary cells than in normal human and rat pituitary cells and higher in invasive pituitary tumor cells than in noninvasive ones. Inhibition of PKC activity has been shown in a variety of tumor cells to inhibit growth in a dose-related fashion. The purpose of the current study was to determine whether hypericin, a potent inhibitor of PKC activity that may be administered clinically, alters the growth and proliferation in established pituitary adenoma lines and to determine if inhibition of PKC activity induces apoptosis, as reported in some other tumor cell types. Two established pituitary adenoma cell lines, AtT-20 and GH4C1, were treated with hypericin in tissue culture for defined periods following passage. Inhibition of growth was found to be dose dependent in all three cell lines in low micromolar concentrations of hypericin, as determined by viable cell counts, methylthiotetrazole assay, and [3H]thymidine uptake studies. Concentrations of hypericin as low as 100 nM also induced apoptosis in these established lines, whereas treatment of normal human fibroblasts with a concentration of 10 microM failed to induce apoptosis. The potential use of hypericin in the therapy of pituitary adenomas warrants additional in vitro investigations with the aim of later moving toward therapeutic trials in selected patients in whom surgical or medical therapy has failed.
蛋白激酶C（PKC）是一种参与多种组织（包括垂体前叶）细胞生长、增殖和分化调节的酶，人们认为它在垂体前叶激素分泌中也发挥作用。研究发现，腺瘤性垂体细胞中的蛋白激酶C活性和表达高于正常人和大鼠的垂体细胞，侵袭性垂体肿瘤细胞中的蛋白激酶C活性和表达高于非侵袭性垂体肿瘤细胞。在多种肿瘤细胞中，抑制PKC活性已被证明可呈剂量依赖性地抑制细胞生长。本研究的目的是确定金丝桃素（一种临床上可能使用的PKC活性强效抑制剂）是否会改变已建立的垂体腺瘤细胞系的生长和增殖，并确定抑制PKC活性是否会像在其他一些肿瘤细胞类型中报道的那样诱导细胞凋亡。在传代后的组织培养中，用金丝桃素对两种已建立的垂体腺瘤细胞系AtT-20和GH4C1进行了特定时间段的处理。通过活细胞计数、甲基硫代四氮唑试验和[3H]胸腺嘧啶核苷摄取研究确定，在低微摩尔浓度的金丝桃素作用下，所有三种细胞系的生长抑制均呈剂量依赖性。低至100 nM的金丝桃素浓度也能诱导这些已建立细胞系发生凋亡，而用10 μM浓度的金丝桃素处理正常人成纤维细胞则未能诱导凋亡。金丝桃素在垂体腺瘤治疗中的潜在用途值得进一步进行体外研究，以期随后对手术或药物治疗失败的特定患者开展治疗试验。
