title: Downregulation of Mcl-1 synergizes the apoptotic response to combined             treatment with cisplatin and a novel fiber chimeric oncolytic adenovirus.
abstract: The aim of this study was to examine the effects of SG511, a novel fiber             chimeric oncolytic adenovirus with E1B 55-kDa deleted, combined with cisplatin             on cancer cells and to identify their underlying mechanisms. The combined effect             of SG511 and cisplatin on HeLa and HT-29 cells was assessed by a crystal violet             assay and an MTT assay, followed by combination index analysis. Cell apoptosis             was evaluated by DAPI staining and visualized by fluorescein-mediated signal detection.             Mitochondrial membrane potential was detected by flow cytometric analysis of Rhodamine             123 accumulation. The activation of the caspase pathway and the expression of             Bcl-2 family proteins were examined by western blotting. Results show that SG511             vector infected various human cancer cell lines and induced growth inhibition             effectively. Of note, SG511 synergistically enhanced the anti-proliferative activity             of cisplatin, a DNA-damaging agent, against HeLa and HT-29 cells in vitro, concomitantly             with increased apoptosis and activation of the mitochondrial pathway. Furthermore,             treatment with SG511 alone or in combination with cisplatin resulted in reduced             expression the anti-apoptotic Bcl-2 family member Mcl-1 in HeLa and HT-29 cells.             Importantly, this combination did not increase the growth inhibitory effects of             cisplatin on human normal liver cells. Collectively, SG511, a novel fiber chimeric             oncolytic adenovirus, sensitizes cancer cells to apoptosis by reducing anti-apoptotic             Mcl-1 protein levels.
authors.affiliation: Institute of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, PR China.
authors.forename: Liangshun
authors.initials: L
authors.lastname: You
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yingming
authors.initials: Y
authors.lastname: Jin
authors.forename: Wenbin
authors.initials: W
authors.lastname: Qian
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D017501:Adenovirus E1B Proteins / Q000172:deficiency / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005434:Flow Cytometry; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
chemical_list: D017501:Adenovirus E1B Proteins; D000970:Antineoplastic Agents; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; D002945:Cisplatin