Lithium ions: A novel treatment for pheochromocytomas and paragangliomas
Lithium ions: A novel treatment for pheochromocytomas and paragangliomas
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DOI：
10.1016/j.surg.2006.12.005
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发表时间：
2007-02-01
期刊：
影响因子：
3.8
通讯作者：
Chen, Herbert
中科院分区：
文献类型：
--
作者：
Kappes, Ashley;Vaccaro, Abram;Chen, Herbert
背景资料。对于嗜铬细胞瘤、副神经节瘤和其他产生儿茶酚胺的肿瘤，手术切除是唯一有效的治疗方法。糖原合成酶激酶30(GSK3β)的激活被认为促进了NE肿瘤的生长和神经内分泌(NE)肽的分泌。因此，我们假设，用著名的GSK3β抑制剂氯化锂(LiCl)抑制这一信号通路可能是控制肿瘤生长和激素产生的潜在治疗策略。用不同浓度的氯化锂(0~30 mM)处理嗜铬细胞瘤PC-12细胞。免疫印迹法检测GSK3β活性和非活性GSK3β、去甲肾上腺素(NE)、嗜铬粒蛋白A(CgA)和Mash 1水平。用四甲基偶氮唑盐比色法检测细胞生长情况。在基线时，PC-12细胞增加了活跃的GSK3β信号。随着LiCl剂量的增加，PC-12细胞对GSK3β的抑制作用呈剂量依赖性。重要的是，LiCl显著抑制了嗜铬细胞瘤细胞的增殖。此外，LiCl对GSK3β的抑制与对CgA和Mash1水平的显著抑制有关。这些数据表明，抑制GSK3β可能是治疗嗜铬细胞瘤和其他儿茶酚胺产品的一种新策略？结冰肿瘤。
Background. Operative resection is the only curative treatment for patients with pheochromocytomas, paragangliomas, and other catecholamine-producing neoplasms. Activation of glycogen synthase kinase 30 (GSK3 beta) is thought to Promote tumor growth and neuroendocrine (NE) peptide secretion in NE, neoplasms. Thus, we hypothesized that inhibition of this signaling pathway with lithium chloride (LiCl), a well-known GSK3 beta inhibitor, could be a potential therapeutic strategy to control tumor growth and hormone production.Methods. Pheochromocytoma PC-12 cells were treated with varying concentrations of LiCl (0 to 30 mM). Levels of active and inactive GSK3 beta and NE peptides chromogranin A (CgA) and Mash 1 were determined by Western blot. Cellular growth was measured by MTT cell-proliferation assay.Results. At baseline, PC-12 cells had increased active GSK3 beta signaling. Treatment of PC-12 cells with increasing dosage's of LiCl resulted in dose-dependent inhibition of GSK3 beta. Importantly, LiCl inhibited pheochromocytoma cellular proliferation significantly. Furthermore, inhibition of GSK3 beta by LiCl was associated with marked suppression of CgA and Mash1 levels.Conclusions. These data suggest that GSK3 beta inhibition may be a novel strategy to treat pheochromocytoma and other catecholamine prod? icing neoplasms.