Abstract
In the present study, we investigated the role of GLUT-1 and PI3K/Akt signaling in radioresistance of laryngeal carcinoma xenografts. Volume, weight, radiosensitization, and the rate of inhibition of tumor growth in the xenografts were evaluated in different groups. Apoptosis was evaluated by TUNEL assay. In addition, mRNA and protein levels of GLUT-1, p-Akt, and PI3K in the xenografts were measured. Treatment with LY294002, wortmannin, wortmannin plus GLUT-1 AS-ODN, and LY294002 plus GLUT-1 AS-ODN after X-ray irradiation significantly reduced the size and weight of the tumors, rate of tumor growth, and apoptosis in tumors compared to that observed in the 10-Gy group (p<0.05). In addition, mRNA and protein expression of GLUT-1, p-Akt, and PI3K was downregulated. The E/O values of LY294002, LY294002 plus GLUT-1 AS-ODN, wortmannin, and wortmannin plus GLUT-1 AS-ODN were 2.7, 1.1, 1.8, and 1.8, respectively. Taken together, these data indicate that GLUT-1 AS-ODN as well as the inhibitors of PI3K/Akt signaling may act as radiosensitizers of laryngeal carcinoma in vivo.
Highlights
Radiotherapy plays an important role in the treatment of early-stage laryngeal carcinoma and laryngeal preservation [1]
We further investigated whether Glucose transporter-1 (GLUT-1) expression and the PI3K/Akt signaling pathway played a role in radioresistance in xenografts of laryngeal carcinoma and whether targeted inhibition of GLUT-1 expression and the PI3K/Akt pathway can enhance the radiosensitivity of laryngeal carcinoma in vivo
Wortmannin plus GLUT-1 antisense oligodeoxynucleotides (AS-ODN) reduced the size of the tumors significantly compared with control after 10 days treatment (p < 0.05)
Summary
Radiotherapy plays an important role in the treatment of early-stage laryngeal carcinoma and laryngeal preservation [1]. There are various methods to improve the effects of radiotherapy, including hyperfractionation[5], concurrent chemoradiotherapy [6], and some radiosensitizers [7], PLOS ONE | DOI:10.1371/journal.pone.0143306. Role of GLUT-1 and PI3K/Akt in Radioresistance of Laryngeal Carcinoma the results of these treatments are unsatisfactory. The mechanism may result from interactions of multiple factors, such as hypoxia, intrinsic radioresistance, including repopulation, tumor-cell proliferation, and DNA damage repair[8]. Several reports have found that targeted inhibition of GLUT-1 expression may suppress the growth and proliferation of cancer cells[14,15,16,17]. We were the first to report a relationship between GLUT-1 expression and radioresistance and revealed that inhibition of GLUT-1 expression by antisense oligodeoxynucleotides (AS-ODN) may improve the radiosensitivity of laryngeal carcinoma, in vitro and in vivo[1]
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