Liu Jun-Jie, Zhang Bao-Fu, Yin Xiao-Xing, Pei Dong-Sheng, Yang Zhi-Xia, Di Jie-Hui, Chen Fei-Fei, Li Hui-Zhong, Xu Wei, Wu Yong-Ping, Zheng Jun-Nian
Nanjing Medical University, Nanjing, China.
J Immunoassay Immunochem. 2012;33(4):352-68. doi: 10.1080/15321819.2012.659782.
RGD peptide (Arg-Gly-Asp tripeptide) binds to integrin αVβ(3) and αVβ(5), which is selectively expressed in tumor neovasculature and on the surface of some tumor cells. Some studies showed that coupling the RGD peptides to anticancer drugs yielded compounds with increased efficiency against tumors and lowered toxicity to normal tissues. The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24) is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive activity without damaging normal cells. To enhance the antitumor effect, we inserted a glycine residue into the wild type (mda-7/IL-24) between (164)Arg and (165)Asp to form a RGD peptide, named RGD-mda-7, then expressed RGD-mda-7 in Escherichia coli. Herein, we describe the expression and purification of RGD-mda-7. We detected the characterizations of immunostimulatory activity, tumor targeting, potent cytopathic effect, and apoptosis inducing exploited by RGD-mda-7 in tumor cells, and also compared these characterizations with wtmda-7/IL-24. The data showed that RGD-mda-7 had more potent tumor targeting and apoptosis-inducing effects than wtmda-7/IL-24.
RGD肽（精氨酸-甘氨酸-天冬氨酸三肽）与整合素αVβ(3)和αVβ(5)结合，这两种整合素在肿瘤新生血管以及一些肿瘤细胞表面选择性表达。一些研究表明，将RGD肽与抗癌药物偶联可产生对肿瘤治疗效率更高且对正常组织毒性更低的化合物。黑色素瘤分化相关基因-7/白细胞介素-24基因（mda-7/IL-24）是一种新型的肿瘤抑制/细胞因子基因，具有强大的肿瘤抑制活性且不损伤正常细胞。为增强抗肿瘤效果，我们在野生型（mda-7/IL-24）的（164）精氨酸和（165）天冬氨酸之间插入一个甘氨酸残基以形成RGD肽，命名为RGD-mda-7，然后在大肠杆菌中表达RGD-mda-7。在此，我们描述RGD-mda-7的表达和纯化。我们检测了RGD-mda-7在肿瘤细胞中发挥的免疫刺激活性、肿瘤靶向性、强大的细胞病变效应和诱导凋亡的特性，并将这些特性与野生型mda-7/IL-24进行比较。数据表明，RGD-mda-7比野生型mda-7/IL-24具有更强的肿瘤靶向性和诱导凋亡作用。
