Deguelin Inhibits the Migration and Invasion of U-2 OS Human Osteosarcoma Cells via the Inhibition of Matrix Metalloproteinase-2/-9 in Vitro

Molecules

Hung-Sheng Shang⁴  Jin-Biou Chang⁴  Ju-Hwa Lin²  Jing-Pin Lin⁵  Shu-Chun Hsu²  Chi-Ming Liu¹  Jia-You Liu⁷  Ping-Ping Wu⁶  Hsu-Feng Lu⁷  Man-Kuan Au³  Jing-Gung Chung² 

[1] Department of Research and Education, Cheng-Hsin General Hospital, No.45, Cheng Hsin St., Pai-Tou, Taipei 112, Taiwan;Department of Biological Science and Technology, China Medical University, No 91, Hsueh-Shih Road, Taichung 404, Taiwan;Department of Orthopedic Surgery, Cheng-Hsin General Hospital, Taipei 112, Taiwan;Department of Pathology, National Defense Medical Center, Division of Clinical Pathology, Tri-Service General Hospital, Taipei 114, Taiwan;School of Chinese Medicine, China Medical University, Taichung 404, Taiwan;School of Pharmacy, China Medical University, Taichung 404, Taiwan;Department of Clinical Pathology, Cheng-Hsin General Hospital, Taipei 112, Taiwan

关键词: deguelin;    U-2OS human osteosarcoma cells;    migration;    invasion;   

DOI  :  10.3390/molecules191016588

来源: mdpi

【 摘 要 】

Osteosarcoma is the most common malignant primary bone tumor in children and young adults and lung metastasis is the main cause of death in those patients. Deguelin, a naturally occurring rotenoid, is known to be an Akt inhibitor and to exhibit cytotoxic effects, including antiproliferative and anticarcinogenic activities, in several cancers. In the present study, we determined if deguelin would inhibit migration and invasion in U-2 OS human osteosarcoma cells. Deguelin significantly inhibited migration and invasion of U-2 OS human osteosarcoma cells which was associated with a reduction of activities of matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases-9 (MMP-9). Furthermore, results from western blotting indicated that deguelin decreased the cell proliferation and cell growth-associated protein levels, such as SOS1, PKC, Ras, PI3K, p-AKT(Ser473), IRE-1α, MEKK3, iNOS, COX2, p-ERK1/2, p-JNK1/2, p-p38; the cell motility and focal adhesion-associated protein levels, such as Rho A, FAK, ROCK-1; the invasion-associated protein levels, such as TIMP1, uPA, MMP-2. MMP-9, MMP-13, MMP-1 and VEGF in U-2 OS cells. Confocal microscopy revealed that deguelin reduced NF-κB p65, Rho A and ROCK-1 protein levels in cytosol. MMP-7, MMP-9 and Rho A mRNA levels were suppressed by deguelin. These in vitro results provide evidence that deguelin may have potential as a novel anti-cancer agent for the treatment of osteosarcoma and provides the rationale for in vivo studies in animal models.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.