Clin Mol Hepatol.  2015 Sep;21(3):257-267. 10.3350/cmh.2015.21.3.257.

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

• Gomes AR
• Abrantes A
• Brito AF
• Laranjo M
• Casalta-Lopes JE
• Goncalves
• Sarmento-Ribeiro AB
• Botelho MF
• Tralhao JG

• KMID: 2351026
• DOI: http://doi.org/10.3350/cmh.2015.21.3.257

Abstract

BACKGROUND/AIMS
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines.
METHODS
Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle.
RESULTS
The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase.
CONCLUSIONS
These results suggest that P53 plays a key role in the radiotherapy response of HCC.

Keyword

Hepatocellular carcinoma; Iodine-131; Radiotherapy; P53

MeSH Terms

Apoptosis/*radiation effects
Blotting, Western
Carcinoma, Hepatocellular/metabolism/pathology/radiotherapy
Cell Line, Tumor
Cell Survival/drug effects
G1 Phase Cell Cycle Checkpoints/radiation effects
*Gamma Rays
Glutathione/metabolism
Hep G2 Cells
Humans
Iodine Radioisotopes/chemistry/pharmacology/therapeutic use
Liver Neoplasms/metabolism/pathology/radiotherapy
Phosphorylation
Reactive Oxygen Species/metabolism
Tumor Suppressor Protein p53/*metabolism
Glutathione
Iodine Radioisotopes
Reactive Oxygen Species
Tumor Suppressor Protein p53