title: HPV16E7 silencing enhances susceptibility of CaSki cells to natural killer cells.
abstract: The aim of the present study was to investigate the cytotoxicity of natural killer (NK) cells to CaSki cells following knockdown of the E7 protein of the human papillomavirus type 16 (HPV16E7). Recombinant adenovirus-short hairpin-E7 protein of the human panillomavirus type 16 (Ad‑sh‑HPV16E7) was constructed and used to infect CaSki cells. The expression of HPV16E7 in CaSki cells was assessed using western blot analysis. The expression of cell surface molecule major histocompatibility complex‑I (MHC‑I) in CaSki cells infected with Ad‑sh‑HPV16E7 was examined using flow cytometry. The cytotoxicity of NK cells isolated and expanded from healthy volunteers on Ad‑sh‑HPV16E7‑infected CaSki cells was assessed using the lactate dehydrogenase (LDH) release assay. Ad‑sh‑HPV16E7 was successfully constructed and able to inhibit HPV16E7 the expression in CaSki cells. The expression of major histocompa-tibility complex I (MHC‑I), a surface molecule, in CaSki cells was increased after infection with Ad‑sh‑HPV16E7. Compared with the controls, the cytotoxicity of NK cells on CaSki cells, which were infected with Ad‑sh‑HPV16E7, was decreased (p<0.05). In conclusion, HPV16E7 suppresses the expression of MHC‑I on CaSki cells to evade cytotoxic T‑cell (CTL) response. However, it was possible to enhance the cytotoxicity of expanded NK cells to cervical cancer cells or HPV16‑infected cells in vitro, indicating that NK cells may be used for immunotherapy of cervical cancer.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Ruili
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Xinlei
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing; D005822:Genetic Vectors / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology*
chemical_list: D015395:Histocompatibility Antigens Class I; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007770:L-Lactate Dehydrogenase