Gondi Christopher S, Rao Jasti S
Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, IL, USA.
Methods Mol Biol. 2009;487:267-81. doi: 10.1007/978-1-60327-547-7_13.
Targeting proteases and their activators would retard the invasive ability of cancer cells, and has been shown to induce apoptosis in certain instances. Various methods have been developed to specifically target protease molecules in an attempt to retard invasion and migration. Of these methods, RNA interference (RNAi) holds great therapeutic potential. RNAi technology is now being used to target specific molecules for use as potential anti-cancer agents. RNAi-mediated silencing is almost catalytic when compared to anti-sense silencing. Of these targets, the uPAR-uPA system and MMPs holds great promise. Targeting uPA/uPAR may provide additive or synergistic treatment benefits if used in combination with conventional therapeutics such as chemotherapy or radiation. Studies point to the fact that specifically targeting MMP-9 or MMP-2 singly or in combination with other proteases could have specific therapeutic implications in the treatment of cancer. In this chapter we discuss the therapeutic potential of siRNA-mediated targeting of the uPAR-uPA system and MMPs as therapeutic agents for the treatment of cancer.
靶向蛋白酶及其激活剂可抑制癌细胞的侵袭能力，并且在某些情况下已显示能诱导细胞凋亡。人们已开发出各种方法来特异性地靶向蛋白酶分子，以试图抑制侵袭和迁移。在这些方法中，RNA干扰（RNAi）具有巨大的治疗潜力。RNAi技术目前正被用于靶向特定分子，以用作潜在的抗癌药物。与反义沉默相比，RNAi介导的沉默几乎具有催化作用。在这些靶点中，尿激酶型纤溶酶原激活物受体-尿激酶型纤溶酶原激活物（uPAR-uPA）系统和基质金属蛋白酶（MMPs）很有前景。如果与化疗或放疗等传统疗法联合使用，靶向uPA/uPAR可能会提供附加或协同的治疗益处。研究表明，单独或与其他蛋白酶联合特异性靶向MMP-9或MMP-2在癌症治疗中可能具有特定的治疗意义。在本章中，我们将讨论小干扰RNA（siRNA）介导的靶向uPAR-uPA系统和MMPs作为癌症治疗药物的治疗潜力。
