Zhang Xuerui, Huo Lina, Jin Haibo, Han Yuheng, Wang Jie, Zhang Yanjun, Lai Xinghuan, Le Ziwei, Zhang Jing, Hua Zichun
The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, Jiangsu, China.
Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou 213164, Jiangsu, China.
Oncotarget. 2017 Jun 27;8(26):42602-42612. doi: 10.18632/oncotarget.16645.
Annexin V, a protein with high affinity to phosphatidylserine (PS) in a calcium dependent manner, has been widely used to probe apoptosis. Annexin V in inhibiting engulfment of apoptotic cells by macrophages had been reported to increase the immunogenicity of tumor cells undergoing apoptosis. However, far less is known about its multiple properties, especially in cancer therapies. Here we found that Annexin V had a good anti-tumor activity in murine melanomaxenograft model. Treatment with Annexin V showed significant reduction in tumor size and remarkable tumor necrosis areas. The serum level of VEGF was downregualted by Annexin V both in normal mice and mice bearing tumor, suggesting that its new role on impeding tumor angiogenesis. In Silico analysis using Oncomine database, we also found the negative correlation of AnnexinV and VEGF both in skin and melanoma. The decreased Annexin V expression shows linearity relation with the elevated VEGF expression. These data provided a possibility that Annexin V can be used as a novel angiogenesis inhibitor in tumor therapy.
膜联蛋白V是一种能以钙依赖方式与磷脂酰丝氨酸（PS）高亲和力结合的蛋白质，已被广泛用于检测细胞凋亡。据报道，膜联蛋白V抑制巨噬细胞对凋亡细胞的吞噬会增加正在经历凋亡的肿瘤细胞的免疫原性。然而，人们对其多种特性了解甚少，尤其是在癌症治疗方面。在这里，我们发现在小鼠黑色素瘤异种移植模型中，膜联蛋白V具有良好的抗肿瘤活性。用膜联蛋白V治疗后，肿瘤大小显著减小，肿瘤坏死区域明显。在正常小鼠和荷瘤小鼠中，膜联蛋白V均下调了VEGF的血清水平，表明其在阻碍肿瘤血管生成方面有新作用。使用Oncomine数据库进行的计算机分析中，我们还发现膜联蛋白V与皮肤和黑色素瘤中的VEGF均呈负相关。膜联蛋白V表达的降低与VEGF表达的升高呈线性关系。这些数据提供了一种可能性，即膜联蛋白V可作为一种新型血管生成抑制剂用于肿瘤治疗。
