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BioMed Research International
Volume 2015 (2015), Article ID 147468, 12 pages
Research Article

RLN2 Is a Positive Regulator of AKT-2-Induced Gene Expression Required for Osteosarcoma Cells Invasion and Chemoresistance

1Department of Spine, The Affiliated Hospital of Qingdao University, Qingdao, China
2Department of Orthopedics, Linyi People’s Hospital, Linyi, Shandong, China
3Department of Dialysis Room, Zhangqiu Hospital of Traditional Chinese Medicine, Zhangqiu, Jinan, China
4Department of Neurology, People’s Hospital of Zhangqiu, Jinan, China

Received 4 April 2015; Revised 9 June 2015; Accepted 11 June 2015

Academic Editor: John D. Wade

Copyright © 2015 Jinfeng Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The aim of the study was to determine the effect of H2 relaxin (RLN2) on invasion, migration, and chemosensitivity to cisplatin in human osteosarcoma U2-OS and MG-63 cells and then to investigate the effect of RLN2 on the AKT/NF-κB signaling pathway. The expression of RLN2, p-AKT (Ser473), and p-ERK1/2 (Phospho-Thr202/Tyr204) proteins was detected by western blot in OS tissues from 21 patients with pulmonary metastatic disease, and the correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated. RLN2 expression was inhibited by RLN2 siRNA transfection in the MG-63 cells. RLN2 was overexpressed in the U2-OS cells by treatment with recombinant relaxin. The results showed that positive relation was found between RLN2 and p-AKT expression in tissues of OS. Silencing RLN2 inhibited cell migratory and invasive ability and angiogenesis formation and increased the chemosensitivity to cisplatin in MG-63 cells. RLN2 overexpression promoted migratory and invasive ability and angiogenesis and increased the chemoresistance to cisplatin in U2-OS cells. Silencing RLN2 inhibited the activity of AKT/NF-κB signaling pathway in MG-63 cells, and vice versa. Blockage of both pathways by specific inhibitors abrogated RLN2-induced survival and invasion of OS cells, and vice versa. Our results indicated RLN2 confers to migratory and invasive ability, angiogenesis, and chemoresistance to cisplatin via modulating the AKT/NF-κB signaling pathway in vitro.