Faculdade de Ciências da Saúde do Trairi, Universidade Federal do Rio Grande do Norte, Santa Cruz, RN, Brazil; Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Departamento de Bioquímica, Universidade Federal do Rio Grande do Norte, Natal, RN, Brazil.
Int J Biol Macromol. 2018 Oct 15;118(Pt B):1470-1478. doi: 10.1016/j.ijbiomac.2018.06.143. Epub 2018 Jun 30.
In this present study, the anti-IIa activity and the antitumor properties of a hybrid heparin/heparan sulfate-like compound (sH/HS) from Litopenaeus vannamei shrimp heads are related. In addition to inhibiting 90.7% of thrombin activity at the lowest tested concentration (0.5 μg/mL), sH/HS compound stimulated the synthesis of antithrombotic heparan sulfate by endothelial cells in a dose-dependent manner. In vitro experiments demonstrated that the molecule from shrimp displayed a potent anti-angiogenic effect, reducing over 80% of the tubular structures formation at 50 and 100 μg/mL. In addition, sH/HS compound was able to inhibit the migration of B16F10 cells at all tested concentrations without affecting the cell viability. Although the studied compound had no effect on the proliferation of such cells during a period of 24 h, it had a significant long-term anti-proliferative effect, reducing about 80% of colony formation and anchorage-independent growth at 50 and 100 μg/mL concentrations. When its effectiveness was tested in vivo, it was demonstrated that sH/HS promoted a reduction of more than 90% of tumor growth. In the context of thromboembolic disorders associated with cancer, such findings make the sH/HS compound an excellent target for studies on inhibiting of development and tumor progression, and the prevention of coagulopathies.
在本研究中，与凡纳滨对虾虾头来源的肝素/硫酸乙酰肝素样杂合化合物（sH/HS）的抗 IIa 活性和抗肿瘤特性有关。sH/HS 化合物在最低测试浓度（0.5μg/mL）下即可抑制 90.7%的凝血酶活性，此外，它还能以剂量依赖的方式刺激内皮细胞合成抗血栓形成的硫酸乙酰肝素。体外实验表明，该虾来源的分子具有很强的抗血管生成作用，在 50 和 100μg/mL 时可使管状结构形成减少 80%以上。此外，sH/HS 化合物能够抑制 B16F10 细胞的迁移，而不影响细胞活力，在所有测试浓度下均如此。虽然在 24 小时的研究期间，该化合物对这些细胞的增殖没有影响，但它对细胞的长期增殖具有显著的抑制作用，在 50 和 100μg/mL 浓度下可使集落形成和锚定非依赖性生长减少约 80%。当在体内测试其有效性时，证明 sH/HS 可促进肿瘤生长减少 90%以上。在与癌症相关的血栓栓塞疾病背景下，这些发现使得 sH/HS 化合物成为抑制肿瘤发展和肿瘤进展以及预防凝血功能障碍的研究的一个极好目标。
