文献类型：期刊文献

英文题名：Cell-penetrating and endoplasmic reticulum-locating TAT-IL-24-KDEL fusion protein induces tumor apoptosis

作者：Zhang, Jian[1];Sun, Aiyou[1];Xu, Rui[1];Tao, Xinyi[1];Dong, Yuguo[1];Lv, Xinxin[1];Wei, Dongzhi[1]

机构：[1]E China Univ Sci & Technol, New World Inst Biotechnol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2016

卷号：231

期号：1

起止页码：84

外文期刊名：JOURNAL OF CELLULAR PHYSIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000362217800011)】；

基金：Contract grant sponsor: National major science and technology projects of China;Contract grant number: 2012ZX09304009.

语种：英文

摘要：Interleukin-24 (IL-24) is a unique IL-10 family cytokine that could selectively induce apoptosis in cancer cells without harming normal cells. Previous research demonstrated that intracellular IL-24 protein induces an endoplasmic reticulum (ER) stress response only in cancer cells, culminating in apoptosis. In this study, we developed a novel recombinant fusion protein to penetrate into cancer cells and locate on ER. It is composed of three distinct functional domains, IL-24, and the targeting domain of transactivator of transcription (TAT) and an ER retention four-peptide sequence KDEL (Lys-Asp-Glu-Leu) that link at its NH2 and COOH terminal, respectively. The in vitro results indicated that TAT-IL-24-KDEL inhibited growth in bladder cancer cells, as well as in non-small cell lung cancer cell line and breast cancer cell line, but the normal human lung fibroblast cell line was not affected, indicating the cancer specificity of TAT-IL-24-KDEL. Western blot analysis showed that apoptosis activation was induced by TAT-IL-24-KDEL through the ER stress-mediated cell death pathway. Treatment with TAT-IL-24-KDEL significantly inhibited the growth of human H460 xenografts in nude mice, and the tumor growth inhibition was correlated with increased hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. These findings suggest that the artificially designed recombinant fusion protein TAT-IL-24-KDEL may be highly effective in cancer therapy and worthy of further evaluation and development. J. Cell. Physiol. 230: 84-93, 2016. (c) 2015 Wiley Periodicals, Inc.