Department of Pharmacology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India.
Department of Pharmacology, Postgraduate Institute of Medical Education and Research and Dr. Ram Manohar Lohia Hospital, New Delhi, India.
J Cancer Res Ther. 2020 Dec;16(Supplement):S84-S89. doi: 10.4103/jcrt.JCRT_737_16.
Zinc, a trace element, is known for downregulating several proangiogenic growth factors and cytokines. However, its antiangiogenic activity is not adequately studied. The present study was aimed to evaluate the possible antiangiogenic activity of zinc via the chick chorioallantoic membrane (CAM) assay. Furthermore, the antiangiogenic activity of the combination therapy of zinc with various doses of sorafenib, a tyrosine kinase inhibitor, was evaluated.
A pilot study was initially conducted so as to select suitable doses of zinc and sorafenib. The antiangiogenic activity after combining zinc 2.5 μg/embryo with sorafenib 1 and 2 μg/embryo was also evaluated. The antiangiogenic activity was quantified in terms of total length of blood vessels, number of junctions, number of branching points, and mean length of the blood vessels.
Zinc 2.5 μg/embryo showed significant (P < 0.05) antiangiogenic activity, as compared to the control group. However, its effect was not comparable to that of sorafenib 2 μg/embryo. The combination of zinc 2.5 μg/embryo with sorafenib 2 μg/embryo did not show an additive/synergistic effect. The combination of zinc 2.5 μg/embryo with sorafenib 1 μg/embryo produced an antiangiogenic activity which was comparable (P > 0.05) to that of sorafenib 2 μg/embryo.
Zinc caused significant antiangiogenic activity in the CAM assay. The lack of addition/synergism in the zinc-sorafenib combination could have been due to the variability in the dose/ratio selection. Addition of zinc to sorafenib therapy could improve treatment tolerability, reduce cost of therapy, and reduce the emergence of drug resistance. Future mechanistic studies could identify the exact pharmacodynamics of zinc as an angiogenesis inhibitor.
锌是一种微量元素，已知其可下调几种促血管生成生长因子和细胞因子。然而，其抗血管生成活性尚未得到充分研究。本研究旨在通过鸡胚尿囊膜（CAM）试验评估锌的可能抗血管生成活性。此外，还评估了锌与不同剂量索拉非尼（一种酪氨酸激酶抑制剂）联合治疗的抗血管生成活性。
首先进行了一项初步研究，以选择合适剂量的锌和索拉非尼。还评估了将锌 2.5μg/胚胎与索拉非尼 1 和 2μg/胚胎联合使用后的抗血管生成活性。血管生成活性通过血管总长度、连接点数、分支点数和血管平均长度来量化。
与对照组相比，锌 2.5μg/胚胎显示出显著的（P<0.05）抗血管生成活性。然而，其效果不如索拉非尼 2μg/胚胎。锌 2.5μg/胚胎与索拉非尼 2μg/胚胎联合使用未显示出相加/协同作用。锌 2.5μg/胚胎与索拉非尼 1μg/胚胎联合使用产生的抗血管生成活性与索拉非尼 2μg/胚胎相当（P>0.05）。
锌在 CAM 试验中引起了显著的抗血管生成活性。锌-索拉非尼联合治疗缺乏相加/协同作用，可能是由于剂量/比例选择的变异性所致。在索拉非尼治疗中加入锌可能会提高治疗耐受性、降低治疗成本并减少耐药性的出现。未来的机制研究可以确定锌作为血管生成抑制剂的确切药效学。
