title: Suppression of human 8-oxoguanine DNA glycosylase (OGG1) augments ultrasound-induced apoptosis in cervical cancer cells.
abstract: Human 8-oxoguanine DNA glycosylase (OGG1) is a major base excision repair enzyme, and it was reported to suppress the activation of intrinsic apoptotic signaling pathway in response to oxidative stress. In this study, our aim was to investigate the effects of OGG1 downregulation on ultrasound-induced apoptosis in cervical cancer cells.
  
  
  
  OGG1 expression was silenced by shRNA in the cervical cancer SW756 and CaSki cells. Cell viability was evaluated by MTT assay after OGG1 knockdown following ultrasound treatment. Ultrasound-induced apoptosis was measured by Annexin V-FITC/propidium iodide. Intracellular reactive oxygen species (ROS) production and Ca(2+) concentration were detected using a fluorescent probe, 2',7'-dichlorofluorescin diacetate (DCFH-DA) and a green fluorescent dye fluo-4AM, respectively. Western blotting was used to analyze the expression of Bcl-2, Bax, cleaved caspase-3, and nuclear factor-κB p65 (NF-κB p65).
  
  
  
  The results indicated that OGG1 knockdown did not suppress cell proliferation, but significantly augmented ultrasound-induced inhibitory effects on the cell viability, and increased ultrasound-induced early apoptosis and late apoptosis and necrosis in the SW756 and CaSki cells when exposure to ultrasound (1MHz) at 1.5W/cm(2) for 30 and 60s. OGG1 knockdown significantly increased intracellular ROS production and Ca(2+) concentration after incubation of 6, 24, and 48h post-ultrasound treatment. The downregulation of Bcl-2 protein and the upregulation of Bax, cleaved caspase-3, and NF-κB p65 protein levels were observed in the shRNA-OGG1 cells and mock-shRNA cells, but no significant change of these protein levels was found between of them.
  
  
  
  These results indicate that downregulation of OGG1 expression can augment ultrasound-induced apoptosis in cervical cancer cells, which suggests that OGG1 suppression might provide a new insight for ultrasound-induced therapeutic effects on cervical cancer treatment.
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Oncology, Han Jiang Group Co. Ltd-Han Jiang Hospital, DanJiangKou 442700, Hubei Province, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Department of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Linjun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Guangmei
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Jiao
authors.affiliation: Department of Ultrasound, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei Province, China. Electronic address: hongxiajing@sina.com.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Jing
mesh_terms: D000814:Aniline Compounds; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D045647:DNA Glycosylases / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000378:metabolism; D005452:Fluoresceins; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014464:Ultrasonic Therapy; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000628:therapy*; D014966:Xanthenes; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; C492760:FITC-annexin A5; C409648:Fluo 4; D005452:Fluoresceins; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014966:Xanthenes; D051028:bcl-2-Associated X Protein; C029569:diacetyldichlorofluorescein; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C505407:CASP3 protein, human; D053148:Caspase 3; D016650:Fluorescein-5-isothiocyanate; D002118:Calcium
keywords: Apoptosis; Cervical cancer cells; OGG1; Reactive oxygen species; Ultrasound