Chen Y, Xu X, Hong S, Chen J, Liu N, Underhill C B, Creswell K, Zhang L
Department of Oncology, Lombardi Cancer Center, Georgetown University Medical School, Washington, DC 20007, USA.
Cancer Res. 2001 Mar 15;61(6):2434-8.
Tachyplesin is an antimicrobial peptide present in leukocytes of the horseshoe crab (Tachypleus tridentatus). In this study, a synthetic tachyplesin conjugated to the integrin homing domain RGD was tested for antitumor activity. The in vitro results showed that RGD-tachyplesin inhibited the proliferation of both cultured tumor and endothelial cells and reduced the colony formation of TSU prostate cancer cells. Staining with fluorescent probes of FITC-annexin V, JC-1, YO-PRO-1, and FITC-dextran indicated that RGD-tachyplesin could induce apoptosis in both tumor and endothelial cells. Western blotting showed that treatment of cells with RGD-tachyplesin could activate caspase 9, caspase 8, and caspase 3 and increase the expression of the Fas ligand, Fas-associated death domain, caspase 7, and caspase 6, suggesting that apoptotic molecules related to both mitochondrial and Fas-dependent pathways are involved in the induction of apoptosis. The in vivo studies indicated that the RGD-tachyplesin could inhibit the growth of tumors on the chorioallantoic membranes of chicken embryos and in syngenic mice.
鲎素是一种存在于中国鲎（Tachypleus tridentatus）白细胞中的抗菌肽。在本研究中，测试了一种与整合素归巢结构域RGD偶联的合成鲎素的抗肿瘤活性。体外实验结果表明，RGD-鲎素抑制培养的肿瘤细胞和内皮细胞的增殖，并减少TSU前列腺癌细胞的集落形成。用FITC-膜联蛋白V、JC-1、YO-PRO-1和FITC-葡聚糖荧光探针染色表明，RGD-鲎素可诱导肿瘤细胞和内皮细胞凋亡。蛋白质免疫印迹法显示，用RGD-鲎素处理细胞可激活半胱天冬酶9、半胱天冬酶8和半胱天冬酶3，并增加Fas配体、Fas相关死亡结构域、半胱天冬酶7和半胱天冬酶6的表达，这表明与线粒体和Fas依赖途径相关的凋亡分子参与了凋亡的诱导。体内研究表明，RGD-鲎素可抑制鸡胚尿囊膜和同基因小鼠体内肿瘤的生长。
