title: The antitumor effects of oncolytic adenovirus H101 against lung cancer.
abstract: Lung cancer is the leading cause of cancer mortality in both men and women, with dismal survival rates due to late-stage diagnoses and a lack of efficacious therapies. The new treatment options with completely novel mechanism of therapeutic activity are needed for lung cancer to improve patient outcome. The present study was aimed at testing the efficacy of recombinant adenovirus H101 as an oncolytic agent for killing human lung cancer cell lines in vitro and in vivo. We assessed the coxsackievirus adenovirus receptor (CAR) expression on human lung cancer cell lines by RT-PCR and immunocytochemistry staining. Viral infectivity and viral replication in lung cancer cells was assayed by flow cytometry and real-time fluorescent quantitative PCR. After H101 treatment, cytotoxic effect, cell cycle progression and apoptosis were further examined by lactate dehydrogenase release assay and flow cytometry in vitro, respectively. In vivo, antitumor effects of H101 were assessed on SCID Beige mice xenografted with human lung cancer cells. Receptor characterization confirmed that human lung cancer cell lines expressed CAR receptor for adenovirus type 5. Lung cancer cells were sensitive to infection by the H101 virus. H101 infection and replication resulted in very potent cytotoxicity, G2/M phase arrest and cell lysis. In vivo, we also showed that H101 significantly inhibited tumor growth following intratumoral injection, with virus replication, cell degeneration and necrosis in the tumor tissue. These results have important implications for the treatment of human lung cancer.
authors.affiliation: Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lei
authors.affiliation: College of Science and Technology, Yunnan Agriculture University, Kunming, Yunnan 650201, P.R. China.
authors.forename: Qi-Hua
authors.initials: QH
authors.lastname: Li
authors.affiliation: Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China.
authors.forename: Ju-Lun
authors.initials: JL
authors.lastname: Yang
authors.affiliation: School of Life Sciences of Yunnan University, Kunming, Yunnan 650091, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China.
authors.forename: Wen-Mang
authors.initials: WM
authors.lastname: Xu
authors.affiliation: Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China.
authors.forename: Wen-Xing
authors.initials: WX
authors.lastname: Zhao
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics* / Q000378:metabolism*; D015316:Genetic Therapy; D057809:HEK293 Cells; D006801:Humans; D015552:Injections, Intralesional; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D050130:Oncolytic Virotherapy / Q000379:methods; D050504:Oncolytic Viruses / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein