Radiation-inducible PTEN expression radiosensitises hepatocellular carcinoma cells.
OBJECTIVE
To test the radiosensitising effects of a tumour-suppressor gene, phosphatase and tensin homologue deleted from chromosome 10 (PTEN), in hepatocellular carcinoma cells (HCC).


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.
Zhang
Yong
Y
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, P. R. China.
Chen
Long-Hua
LH
Wang
Li
L
Wang
Hong-Mei
HM
Zhang
Yao-Wei
YW
Shi
Yu-Sheng
YS
D017209:Apoptosis / Q000528:radiation effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D016195:G2 Phase / Q000528:radiation effects; D015870:Gene Expression / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D058539:Phosphatidylinositol 3-Kinase / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects; D011836:Radiation Tolerance / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D013997:Time Factors; D014965:X-Rays / Q000009:adverse effects*
D058539:Phosphatidylinositol 3-Kinase; D017346:Protein Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human