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Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma cells.
- Source :
-
International Journal of Radiation Biology . Nov2010, Vol. 86 Issue 11, p964-974. 11p. 2 Black and White Photographs, 6 Graphs. - Publication Year :
- 2010
-
Abstract
- Purpose: To test the radiosensitising effects of a tumour-suppressor gene, phosphatase and tensin homologue deleted from chromosome 10 (PTEN), in hepatocellular carcinoma cells (HCC). Materials and methods: Radiation-induced wild-type PTEN or mutant PTEN was transfected into the SMMC-7721 human hepatocellular carcinoma cells. The expressions of PTEN and serine/threonine protein kinase (Akt) were detected by Western blot analysis. 3-(4,5)-dimethylthiahiazo-(-z-y1)- 3,5-di-phenytetrazoliumromide (MTT) absorbance and clonogenic survival assays were used to determine cell viability, proliferation and radiosensitivity. By performing cell-cycle analysis, terminal deoxynucleotidyltransferase (TdT)-mediated dUTP biotin nick end labelling (TUNEL) assays and gamma-histone H2A (γ-H2AX) formation assays, we were able to explore the mechanism of PTEN enhancement of radiosensitivity. Results: Restoration of wild-type PTEN induced growth suppression and sensitised the cells to ionising radiation specifically by its lipid phosphatase activity through the PTEN-phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathway. Restoring PTEN function correlated with G2/M arrest, apoptosis and the retardation of repair of radiation-induced double strand breaks (DSB). Conclusions: Our study suggests that strategies designed to restore the expression of PTEN may represent promising new therapies for sensitising HCC cells to ionising radiation. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RADIATION
*LIVER cancer
*TUMOR suppressor genes
*PHOSPHATASES
*PROTEIN kinases
Subjects
Details
- Language :
- English
- ISSN :
- 09553002
- Volume :
- 86
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- International Journal of Radiation Biology
- Publication Type :
- Academic Journal
- Accession number :
- 54865682
- Full Text :
- https://doi.org/10.3109/09553002.2010.496032