title: Inhibition of antiviral drug cidofovir on proliferation of human papillomavirus-infected cervical cancer cells.
abstract: In order to evaluate the potential application value of cidofovir (CDV) in the prevention of human papillomavirus (HPV) infection and treatment of cervical cancer, the inhibitory effect of CDV on the proliferation of HPV 18-positive HeLa cells in cervical cancer was preliminarily investigated, using cisplatin (DDP) as a positive control. An MTT assay was used to analyze the effects of CDV and DDP on HeLa cell proliferation. In addition, clone formation assay and Giemsa staining were used to examine the extent of HeLa cell apoptosis caused by CDV and DDP. Flow cytometry was also used to detect the shape and size of apoptotic cells following propidium iodide staining, while western blot analysis identified the expression levels of of E6 and p53 proteins in HeLa cells. A cell climbing immunofluorescence technique was used to locate the subcellular position of p53 in HeLa cells. The results demonstrated that CDV and DDP inhibited the proliferation of HeLa cells in a concentration- and time-dependent manner. Flow cytometry showed that CDV and DDP treatments resulted in cell arrest in the S-phase, and triggered programmed cell death. Furthermore, western blot analysis revealed that CDV and DDP inhibited E6 protein expression and activated p53 expression in HeLa cells. Finally, the immunofluorescence results indicated that CDV and DDP inhibited the nuclear export of p53 by E6 protein, which is required for degradation of endogenous p53 by MDM2 and human papilloma virus E6. In conclusion, CDV and DDP inhibited HeLa cell proliferation in a concentration- and time-dependent manner, reduced the expression of E6 protein, and reinstated p53 protein activity. Thus, CDV regulates cell cycle arrest and apoptosis, and may be a potential cervical cancer therapeutic strategy.
authors.affiliation: Department of Infectious Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China; Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China; Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Experiment Teaching Center of Clinical Medicine, Chengdu College of Medicine, Chengdu, Sichuan 610500, P.R. China.
authors.forename: Lv-Xia
authors.initials: LX
authors.lastname: Dai
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Microbiology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Nana
authors.initials: N
authors.lastname: Ding
authors.affiliation: Department of Infectious Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Infectious Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Ming-Yuan
authors.initials: MY
authors.lastname: Li
authors.affiliation: Department of Microbiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
authors.forename: Bao-Ning
authors.initials: BN
authors.lastname: Wang
authors.affiliation: Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China.
authors.forename: Xin-Li
authors.initials: XL
authors.lastname: Shi
authors.affiliation: Department of Infectious Disease, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
authors.forename: Hua-Bing
authors.initials: HB
authors.lastname: Tan
keywords: HeLa cells; apoptosis; cervical cancer; cidofovir; cisplatin; human papillomavirus