title: Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo.
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.
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Xing-Mei
authors.initials: XM
authors.lastname: Luo
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Min-Li
authors.initials: ML
authors.lastname: Zhou
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Bao
authors.affiliation: Department of Otolaryngology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Shui-Hong
authors.initials: SH
authors.lastname: Zhou
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang Province, 310003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Radiotherapy, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, 310003, China.
authors.forename: Zhong-Jie
authors.initials: ZJ
authors.lastname: Lu
mesh_terms: D000730:Androstadienes / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D051272:Glucose Transporter Type 1 / Q000235:genetics*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011836:Radiation Tolerance; D015398:Signal Transduction / Q000187:drug effects; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D000077191:Wortmannin; D014965:X-Rays; D023041:Xenograft Model Antitumor Assays
chemical_list: D000730:Androstadienes; D002867:Chromones; D051272:Glucose Transporter Type 1; D009025:Morpholines; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin