title: The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway.
abstract: We reported in an earlier study that using mass spectrometry and bioinformatic analysis demonstrated Rac1 protein might be mostly mitochondrial target in the radiosensitization process of nasopharyngeal carcinoma CNE-1 cells. The goal of our current study was to reveal the relationship between Rac1/NADPH pathway and radiosensitization in CNE-1 cells using Rac1 activator, phorbol 12-myristate 13-acetate (PMA) and Rac1 inhibitor NSC23766. The Rac1-GTP expression was determined using a pulldown assay, the Rac1 location using a immunofluorescence with a laser scanning confocal microscope, the NADPH oxidase activity with NBT assay and the reactive oxygen species with DCFH-DA probe. The apoptosis rate was analyzed by flow cytometry, and the expressions of p67(phox) and NFκB-p105/p50 were analyzed by Western blot. After treatment with PMA and 2 Gy radiation (compared to the control), Rac1-GTP was activated and translocated to the cell membrane. NADPH oxidase activity, reactive oxygen species of intracellular concentration and the apoptosis rate increased significantly. The expression of p67(phox) and NFκB-p50 protein also increased. However, in the cells treated with NSC23766 alone or NSC23766 combined with 2 Gy irradiation, the results were just the opposite. Overall, these results indicate that the Rac1 protein may be the key target involved in the radiosensitization of nasopharyngeal carcinoma cells. The activated Rac1/NADPH pathway combined with radiation can increase the radiosensitivity of nasopharyngeal carcinoma cells, and the Rac1/NADPH pathway may be the signaling pathway involved in the radiosensitization process.
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Chunmiao
authors.initials: C
authors.lastname: Wang
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Pan
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Hou
authors.affiliation: b   Department of Basic Research, Guangxi Institute for Cancer Research, Nanning, 530021, China.
authors.forename: Danrong
authors.initials: D
authors.lastname: Li
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Mo
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Mo
authors.affiliation: a   College of Pharmacy, Guangxi Medical University, Nanning 530021, China; and.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002277:Carcinoma; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009249:NADP / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology*; D010750:Phosphoproteins / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D011743:Pyrimidines / Q000494:pharmacology; D011836:Radiation Tolerance; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014965:X-Rays; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D016328:NF-kappa B; C487513:NSC 23766; D010750:Phosphoproteins; D011743:Pyrimidines; D017382:Reactive Oxygen Species; C079789:neutrophil cytosol factor 67K; D009249:NADP; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein; D013755:Tetradecanoylphorbol Acetate