ABSTRACT

Heparan sulfate proteoglycans (HSPGs) play important roles in cancer initiation and progression, by interacting with the signaling pathways that affect proliferation, adhesion, invasion and angiogenesis. These roles suggest the possibility of various strategies of regulation of these molecules. In this review, we demonstrated that the anticancer drugs can regulate the heparan sulfate proteoglycans activity in different ways: some act directly in core protein, and can bind to a specific type of HSPG. Others drugs interact with glycosaminoglycans chains, and others can act directly in enzymes that regulate HSPGs levels. We also demonstrated that the HSPGs drug targets can be divided into four groups: monoclonal antibodies, antitumor antibiotic, natural products, and mimetics peptide. Interestingly, many drugs demonstrated in this review are approved by FDA and is used in cancer therapy (Food and Drug Administration) like trastuzumab, panitumumab, bleomycin and bisphosphonate zoledronic acid (ASCO) or are in clinical trials like codrituzumab and genistein. This review should help researchers to understand the mechanism of action of anticancer drugs existing and also may inspire the discovery of new drugs that regulate the heparan sulfate proteoglycans activity.

摘要

硫酸乙酰肝素蛋白聚糖 (HSPG) 通过与影响增殖、粘附、侵袭和血管生成的信号通路相互作用，在癌症的发生和进展中发挥重要作用。这些作用表明调节这些分子的各种策略的可能性。在这篇综述中，我们证明了抗癌药物可以以不同的方式调节硫酸乙酰肝素蛋白聚糖的活性：一些直接作用于核心蛋白，并且可以与特定类型的 HSPG 结合。其他药物与糖胺聚糖链相互作用，其他药物可以直接作用于调节 HSPG 水平的酶。我们还证明了 HSPGs 药物靶点可以分为四组：单克隆抗体、抗肿瘤抗生素、天然产物和模拟肽。有趣的是，本次审查中展示的许多药物已获得 FDA 批准并用于癌症治疗（食品和药物管理局），如曲妥珠单抗、帕尼单抗、博来霉素和双膦酸盐唑来膦酸 (ASCO)，或正在临床试验中，如 codrituzumab 和染料木黄酮。该综述应有助于研究人员了解现有抗癌药物的作用机制，也可能会启发发现调节硫酸乙酰肝素蛋白多糖活性的新药物。