PMID- 26350185
OWN - NLM
STAT- MEDLINE
DCOM- 20160111
LR  - 20171213
IS  - 2038-2529 (Electronic)
IS  - 0300-8916 (Linking)
VI  - 101
IP  - 5
DP  - 2015 Sep-Oct
TI  - Inhibition of hypoxia-inducible factor-1 alpha radiosensitized MG-63 human 
      osteosarcoma cells in vitro.
PG  - 578-84
LID - 10.5301/tj.5000243 [doi]
AB  - AIMS AND BACKGROUND: Hypoxia is a fundamental microenvironmental component of 
      osteosarcoma which induces activation of the hypoxia-inducible factor-1 (HIF-1) 
      pathway. Overexpression of HIF-1alpha has been linked to tumor resistance to radio- 
      or chemotherapy. However, little is known about the effects of HIF-1alpha inhibition 
      on hypoxic radioresistance of human osteosarcoma cells. Here, we investigated the 
      effects of HIF-1alpha inhibition on cell survival and radiosensitivity in the MG-63 
      human osteosarcoma cell line. METHODS: HIF-1alpha inhibition was achieved by small 
      interfering RNA (siRNA) targeting of HIF-1alpha or via chetomin. Inhibition of the 
      HIF-1 pathway was determined by monitoring the expression levels of HIF-1alpha, 
      carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) using 
      quantitative real-time PCR and Western blot analyses. Clonogenic assay was 
      performed after irradiation (2-10 Gy) to investigate the effect of HIF-1alpha 
      inhibition on the radiosensitivity of human osteosarcoma cells under normoxic and 
      hypoxic conditions. RESULTS: Compared to the control groups, treatment with 
      HIF-1alpha siRNA or chetomin significantly reduced the hypoxia-inducible 
      radioresistance of MG-63 cells. However, siRNA and chetomin showed different 
      effects on the radiosensitivity under normoxic conditions. CONCLUSIONS: Our 
      results indicate that inhibition of HIF-1alpha effectively decreases hypoxia-induced 
      transcription and radiosensitizes hypoxic MG-63 human osteosarcoma cells in 
      vitro.
FAU - Jin, Zhu
AU  - Jin Z
AD  - Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - 
      China.
FAU - Aixi, Yu
AU  - Aixi Y
AD  - Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - 
      China.
FAU - Baiwen, Qi
AU  - Baiwen Q
AD  - Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - 
      China.
FAU - Zonghuan, Li
AU  - Zonghuan L
AD  - Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - 
      China.
FAU - Xiang, Hu
AU  - Xiang H
AD  - Department of Micro-Orthopedics, Zhongnan Hospital of Wuhan University, Wuhan - 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150804
PL  - United States
TA  - Tumori
JT  - Tumori
JID - 0111356
RN  - 0 (Disulfides)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Indole Alkaloids)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 1403-36-7 (chetomin)
SB  - IM
MH  - Blotting, Western
MH  - Bone Neoplasms/*physiopathology/radiotherapy
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Disulfides/*pharmacology
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors/*metabolism
MH  - Indole Alkaloids/*pharmacology
MH  - Osteosarcoma/*physiopathology/radiotherapy
MH  - RNA, Small Interfering/*pharmacology
MH  - *Radiation Tolerance/drug effects
MH  - Radiation-Sensitizing Agents/*pharmacology
MH  - Real-Time Polymerase Chain Reaction
MH  - Up-Regulation
EDAT- 2015/09/10 06:00
MHDA- 2016/01/12 06:00
CRDT- 2015/09/10 06:00
PHST- 2014/12/31 00:00 [accepted]
PHST- 2015/09/10 06:00 [entrez]
PHST- 2015/09/10 06:00 [pubmed]
PHST- 2016/01/12 06:00 [medline]
AID - 168571F1-81C5-4BCB-A9E5-5758E089DC14 [pii]
AID - 10.5301/tj.5000243 [doi]
PST - ppublish
SO  - Tumori. 2015 Sep-Oct;101(5):578-84. doi: 10.5301/tj.5000243. Epub 2015 Aug 4.