Expression of the RIP-1 Gene and its Role in Growth and Invasion of Human Gallbladder Carcinoma

Cellular Physiology and Biochemistry

关键词: Invasion;    Xenograft tumor;    Gallbladder cancer;    Receptor interacting protein-1;    siRNA;    growth;   

DOI  :  10.1159/000366328

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background and Aim Receptor interacting protein(RIP)-1 is thought to have a significant role in inflammation signaling pathways; however, the role of RIP-1 in malignant tumors is largely unknown. Methods The present study examined the functions and underlying mechanisms of RIP-1 in gallbladder cancer in vitro and in vivo. In this study we determined the expression and role of RIP-1 in 60 clinical specimens from patients with gallbladder cancer and 3 gallbladder cancer cell lines. Using siRNA targeting RIP-1, plasmid vectors (phU6-EGFP-puro/siRIP-1) were constructed and transfected into the gallbladder cells to characterize the biological effect of RIP-1. Results In vitro experiments indicated that silencing of RIP-1 in NOZ cells significantly suppressed growth and invasion. Furthermore, silencing of RIP-1 affected the RIP1-NF-κB/c-jun(AP-1)-VEGF-C pathways in NOZ cells. Silencing of RIP-1 in vivo inhibited tumor growth in a NOZ cell subcutaneous xenograft model. Immunohistochemstry analysis of the tumor in thesubcutaneous xenograft model also suggested that RIP-1 mediates the expression of VEGF-C. Conclusion We have elucidated therelationship between RIP-1 overexpression and the growth and invasion of gallbladder cancer from clinical specimens using a xenograft model. We provide evidence that a reduction in the expression of RIP-1 in gallbladder cancer cells can exert inhibitory effects on the ability of cells to grow and invade in vitro. Thus, targeting RIP-1may be useful in the treatment of gallbladder cancer.

【 授权许可】

CC BY-NC-ND