期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 34, 期 4, 页码 1152-1165出版社
KARGER
DOI: 10.1159/000366328
关键词
Gallbladder cancer; Receptor interacting protein-1; siRNA, growth; Invasion; Xenograft tumor
资金
- National Natural Science Foundation of China [81272373]
- Key Project of Science and Technology Research Program in Fujian Province [2009Y0024]
- Key Project of Science Research in Fujian Medical University [09ZD017]
- National Clinical Key Specialty Construction Project (General Surgery) of China
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-kappa B/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-1 may be useful in the treatment of gallbladder cancer.
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