This study aims to elucidate the role of radiation induces Akt expression in regulatory T cells (Tregs). The surgically removed BCa tissue was collected from 26 patients treated with or without radiotherapy. The frequency of Tregs and apoptotic Tregs in BCa tissue was assessed by
flow cytometry. A cell culture model was employed to investigate the mechanism by which the tumour-infiltrating Tregs survive from radiation. After radiotherapy, the frequency of Treg was increased in the BCa tissue; the apoptotic Tregs were decreased; the expression of Akt was increased in remained Tregs. The results were reproduced in vitro with a cell culture model. The addition of Akt inhibitor blocked the radiation-induced Treg survival in Adriamycin culture. Akt plays an important
MI-503 manufacturer role in the radiation-induced tumour-infiltrating Treg survival in BCa. The bladder carcinoma (BCa) is the fifth most common cancer, which accounts for 85-90% of the primary carcinomas with increasing incidence worldwide [1, 2]. Although the research on BCa was advanced rapidly in the last decade, the pathogenesis of BCa remains unknown; the prognosis of patients with BCa is unsatisfactory [3]. Regulatory T cells (Tregs) are a subtype of T cells. A majority of Tregs is CD4+ CD25+ Foxp3+ Tregs [4]. Tregs express a set of immune suppressive molecules, such as transforming growth factor (TGF)-β and interleukin (IL)-10, to suppress other effector T cells’ activities [5]. Thus, Tregs are an important cell population in the maintenance of homoeostasis in the body. On the other hand, Tregs also suppress the activities of the antitumour immune cells, such as cytotoxic CD8+ T cells [6]; cancer cells thus get the chance to grow. Some investigators propose to get rid of Tregs from the body, using monoclonal anti-CD25
antibodies to promote the therapeutic effect of cancer Ribonuclease T1 [7]. How the increase in tumour-infiltrating Tregs occurs is unclear. Protein kinase B is also known as Akt. Akt is a serine/threonine protein kinase that plays an important role in a number of cellular processes such as glucose metabolism, cell proliferation, apoptosis, transcription and cell migration. Cumulative reports indicate that Akt plays an important role in cancer cell survival [8]. Direct inhibition of the serine/threonine kinase Akt provides another avenue to pharmacologically suppress tumour cells’ activity [9]. Yet, whether the expression of Akt in cancer tissue has any association with Treg survival is unclear. Thus, we collected surgically removed BCa tissue and found an increase in Akt expression in the tumour-infiltrating Tregs, which greatly promoted the Treg’s survival. Reagents. The fluorescently labelled antibodies were purchased from BD Bioscience (Shanghai, China). Monoclonal antibodies of Foxp3, CD4, CD25, Akt, CD3 and CD28 were purchased from Santa Cruz Biotech (Santz Cruz, CA, USA).