title: Role of mimic of manganese superoxide dismutase in proliferation and apoptosis of gastric carcinoma BGC-823 cells in vitro and in vivo.
abstract: The aim of this study was to investigate the anti-cancer effect and mechanism of mimic of manganese superoxide dismutase (MnSODm) in gastric carcinoma cells in vitro and in vivo. The MTT was used to measure cytotoxicity of the MnSODm. The appearance of apoptotic BGC-823 cells was detected by flow cytometry analysis. Apoptosis proteins, caspase family and Bcl-2 family were viewed by Western blotting. The phosphoinositide 3 kinase (PI3K)/Akt signaling pathway and the NF-κB pathway were also examined. PI3K inhibitor LY294002 was used to examine the involvement of the PI3K/Akt signaling pathway in this apoptosis-inducing effect. BGC-823 cell xenograft serious combined immunodeficiency disease mice were used for the in vivo study. The result showed that MnSODm could induce growth arrest and apoptosis of BGC-823 cells in vitro and in vivo. Further analysis demonstrated the involvement of activation of caspase cascade in MnSODm induced apoptosis. The expression of anti-apoptotic Bcl-2 was decreased, whereas the expression of pro-apoptotic Bax protein was increased. The main mechanisms on MnSODm-induced apoptosis were related to the inhibition of PI3K expression, which inactivated the phosphorylation of Akt involving the prevention of NF-κB phosphorylation and nuclear translocation. This phenomenon could be inhibited by the PI3K inhibitor LY294002. We demonstrated that the mechanisms of MnSODm inhibited the BGC-823 cell proliferation in vitro primarily are related to the induced apoptosis, which appears to be regulated by the PI3K/Akt pathway involving the prevention of NF-κB nuclear translocation, and then triggering the activation of the caspase cascades. Moreover, the anticancer effect in vivo on BGC-823 cells xenografted mice was also due to MnSODm-mediated apoptosis.
authors.affiliation: Department of Pharmacy, Gansu provincial Hospital, Lanzhou 730000, Gansu, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Ultrasound, Gansu provincial Hospital, Lanzhou 730000, Gansu, China.
authors.forename: Zu-Bang
authors.initials: ZB
authors.lastname: Zhou
authors.affiliation: Division of Oncology, Gansu provincial Hospital, Lanzhou 730000, Gansu, China.
authors.forename: Chang-An
authors.initials: CA
authors.lastname: Guo
authors.affiliation: Department of Pharmacy, Gansu provincial Hospital, Lanzhou 730000, Gansu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhai
authors.affiliation: Division of Oncology, Gansu provincial Hospital, Lanzhou 730000, Gansu, China.
authors.forename: Fa-Mei
authors.initials: FM
authors.lastname: Qi
authors.affiliation: Division of Oncology, Gansu provincial Hospital, Lanzhou 730000, Gansu, China. Electronic address: lhl862010@126.com.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D023041:Xenograft Model Antitumor Assays
chemical_list: D002867:Chromones; D009025:Morpholines; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D013482:Superoxide Dismutase; D051058:Oncogene Protein v-akt; D020169:Caspases
keywords: Apoptosis; BGC-823 cells; Mimic of manganese superoxide dismutase; NF-κB; Phosphoinositide 3 kinase/Akt; Xenograft mouse model