Up-regulated isocitrate dehydrogenase 1 suppresses proliferation, migration and invasion in osteosarcoma: in vitro and in vivo

Xiang Hu; Yang Liu; Chunxia Qin; Zhenyu Pan; Jun Luo; Aixi Yu; Zhen Cheng

doi:10.1016/j.canlet.2013.12.020

Up-regulated isocitrate dehydrogenase 1 suppresses proliferation, migration and invasion in osteosarcoma: in vitro and in vivo

Cancer Lett. 2014 Apr 28;346(1):114-21. doi: 10.1016/j.canlet.2013.12.020. Epub 2013 Dec 22.

Authors

Xiang Hu¹, Yang Liu², Chunxia Qin², Zhenyu Pan³, Jun Luo⁴, Aixi Yu⁵, Zhen Cheng⁶

Affiliations

¹ Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China; Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA.
² Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA.
³ Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
⁴ Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
⁵ Department of Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address: yuaixi666@hotmail.com.
⁶ Molecular Imaging Program at Stanford, Canary Center at Stanford for Cancer Early Detection, Department of Radiology and Bio-X Program, Stanford University, Stanford, CA, USA. Electronic address: zcheng@stanford.edu.

Abstract

Very few studies have been reported the function of wild type IDH1 in tumor progress. Previously, we reported that IDH1 correlated with pathological grade and metastatic potential inversely in human osteosarcoma. Here, IDH1 was found lower expressed in osteosarcoma tissues than that of adjacent normal bone tissues. In addition, we observed in vitro anti-proliferation and pro-apoptosis effects of up-regulated IDH1 on osteosarcoma cell lines. The migration and invasion activity was also markedly reduced by IDH1 up-regulation. Unexpectedly, IDH1 up-regulation also suppressed tumor growth and metastasis in vivo. Therefore, IDH1 may represent a potential novel treatment and preventive strategy for osteosarcoma.

Keywords: Invasion; Isocitrate dehydrogenase 1; Migration; Osteosarcoma; Proliferation.

MeSH terms

Animals
Apoptosis / physiology
Blotting, Western
Bone Neoplasms / enzymology*
Bone Neoplasms / pathology
Cell Line, Tumor
Cell Movement* / physiology
Cell Proliferation*
Flow Cytometry
Heterografts
Humans
Immunohistochemistry
Isocitrate Dehydrogenase / metabolism*
Male
Mice
Mice, Nude
Neoplasm Invasiveness
Osteosarcoma / enzymology*
Osteosarcoma / pathology
Real-Time Polymerase Chain Reaction
Up-Regulation

Substances

Isocitrate Dehydrogenase
IDH1 protein, human

Grants and funding

P30 CA124435/CA/NCI NIH HHS/United States