Akt Promotes Irradiation-Induced Regulatory T-Cell Survival in Hepatocellular Carcinoma

Abstract Background Radiotherapy is an efficient remedy in the treatment of hepatocellular carcinoma (Hca); however, some cancer cells can still survive from the radiation and the therapeutic effect is to be improved. Regulatory T cell (Tregs)–induced tumor tolerance and Akt expression play importan...

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Bibliographic Details
Published in:The American journal of the medical sciences 2013-08, Vol.346 (2), p.123-127
Main Authors: Li, Chuan-Gang, MD, PhD, Wu, Feng-Lin, MD, PhD, Li, Ying-Jia, MD, PhD, He, Mei-Rong, MD, PhD, Sun, Ai-Min, MD, PhD
Format: Article
Language:English
Subjects:
Akt
AKT protein
Animals
Apoptosis
Carcinoma, Hepatocellular - metabolism
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Hepatocellular carcinoma
Internal Medicine
Liver
Liver Neoplasms - metabolism
Liver Neoplasms, Experimental
Proto-Oncogene Proteins c-akt - antagonists & inhibitors
Proto-Oncogene Proteins c-akt - genetics
Proto-Oncogene Proteins c-akt - metabolism
Radiotherapy
Rats
Rats, Inbred BUF
Regulatory T cell
T-Lymphocytes, Regulatory - metabolism
T-Lymphocytes, Regulatory - radiation effects
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Summary:Abstract Background Radiotherapy is an efficient remedy in the treatment of hepatocellular carcinoma (Hca); however, some cancer cells can still survive from the radiation and the therapeutic effect is to be improved. Regulatory T cell (Tregs)–induced tumor tolerance and Akt expression play important roles in the tumor survival. This study aims to elucidate the role of radiation induces Akt expression in Tregs. Methods A rat Hca model was developed. Hca tissue was collected from the rats with or without radiotherapy. The frequency of Treg and apoptotic Treg in Hca tissue was assessed by flow cytometry. A cell culture model was used to investigate the mechanism by which the tumor-infiltrating Tregs survive from irradiation. Results After radiotherapy, the frequency of Treg was increased in Hca, the frequency of apoptotic Tregs was decreased and the expression of Akt was increased in the remaining Tregs. The results were reproduced in vitro with a cell culture model. The addition of Akt inhibitor blocked the irradiation-induced Treg survival. Tregs with high levels of Akt still preserve the immune suppressor function. Conclusions Akt plays an important role in the radiation-induced tumor-infiltrating Treg survival in Hca.
ISSN:0002-9629
1538-2990
DOI:10.1097/MAJ.0b013e31826ceed0