Zheng Donghang, Chen Hao, Davids Jennifer, Bryant Marsha, Lucas Alexandra
Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, FL, USA.
Cardiovasc Hematol Disord Drug Targets. 2013 Aug;13(2):123-32. doi: 10.2174/1871529x11313020005.
Serine protease inhibitors (Serpins) play an important role in regulating a wide array of diverse biological activities, representing up to 2-10% of circulating plasma proteins. The serpin suicide inhibitors regulate coagulation (thrombosis and thrombolysis), neurotrophic factors, hormone transport, complement and inflammation, angiogenesis, hormone transport, and blood pressure among many other biological reactions. Select serpins have been associated with progression or remission of selected cancers, making them valuable for therapeutic or diagnostic use. Plasminogen activator inhibitor-1 (PAI-1), the main regulator of thrombolysis, has the potential to either reduce or accelerate tumor growth but blockade of PAI-1 has recently been reported to reduce cancer cell migration, proliferation and survival through modulating the function of urokinase-type plasminogen activator receptor. Maspin is a non-inhibitory serpin, that increases cancer cell sensitivity to apoptosis and inhibits cancer cell migration thus providing a serpin that blocks tumor gorwth. Pigment epithelium derived factor (PEDF) has potent anti-angiogenesis activity and also promotes cancer cell apoptosis. Among other serpins, the mammalian serpin, neuroserpin, and the myxomavirus derived serpin, Serp-1 are under investigation in our lab for their potential tumor-suppressive functions. Further study on the efficacy and mechanisms of serpin mediated anti-cancer activity is warranted in order to develop new serpin-based approaches in cancer therapy.
丝氨酸蛋白酶抑制剂（Serpins）在调节多种不同的生物活性中发挥着重要作用，占循环血浆蛋白的2%-10%。丝氨酸蛋白酶抑制剂自杀性抑制剂调节凝血（血栓形成和溶栓）、神经营养因子、激素运输、补体和炎症、血管生成、激素运输以及血压等许多其他生物反应。某些丝氨酸蛋白酶抑制剂已与特定癌症的进展或缓解相关，这使得它们在治疗或诊断方面具有价值。纤溶酶原激活物抑制剂-1（PAI-1）是溶栓的主要调节因子，具有降低或加速肿瘤生长的潜力，但最近有报道称，阻断PAI-1可通过调节尿激酶型纤溶酶原激活物受体的功能来减少癌细胞的迁移、增殖和存活。Maspin是一种非抑制性丝氨酸蛋白酶抑制剂，可增加癌细胞对凋亡的敏感性并抑制癌细胞迁移，从而提供一种可阻断肿瘤生长的丝氨酸蛋白酶抑制剂。色素上皮衍生因子（PEDF）具有强大的抗血管生成活性，还可促进癌细胞凋亡。在其他丝氨酸蛋白酶抑制剂中，我们实验室正在研究哺乳动物丝氨酸蛋白酶抑制剂、神经丝氨酸蛋白酶以及黏液瘤病毒衍生的丝氨酸蛋白酶抑制剂Serp-1的潜在肿瘤抑制功能。有必要进一步研究丝氨酸蛋白酶抑制剂介导的抗癌活性的疗效和机制，以便开发基于丝氨酸蛋白酶抑制剂的癌症治疗新方法。
