title: N‑Myc downstream‑regulated gene 2 suppresses the proliferation of T24 human bladder cancer cells via induction of oncosis.
abstract: Previous studies have reported the antitumor activity of N‑Myc downstream‑regulated gene 2 (NDRG2), a novel p53‑inducible gene, in several types of cancer. The present study aimed to investigate the effects of NDRG2 expression on the proliferation of a human bladder cancer cell line. NDRG2 and control green fluorescent protein (GFP) recombinant adenovirus plasmids were constructed and transfected into a bladder cancer cell line with mutant p53 (T24 cells). NDRG2 expression was analyzed using western blot analysis and immunofluorescence assay (IFA); in addition, the subcellular localization of NDRG2 was detected using a confocal microscope. The proliferation rate of cells was measured using colony formation and MTT assays. Furthermore, the cell cycle of transfected T24 cells was detected by flow cytometry. The results indicated that T24 cells expressed low levels of NDRG2 prior to infection with GFP‑NDRG2 recombinant adenovirus; by contrast, following infection, NDRG2 was primarily overexpressed in mitochondria. The proliferation rate of T24 cells was significantly reduced by NDRG2 expression (P<0.01). In addition, 82.1% of NDRG2‑expressing cells were in S‑phase, compared to 74.4% in the control virus‑infected cells (P<0.05). Furthermore, upregulation of NDRG2 induced an increase in oncosis, rather than apoptosis, in T24 cell. In conclusion, the results of the present study indicated that NDRG2 expression in mitochondria may arrest bladder cancer cells in S‑phase as well as decrease cell proliferation through inducing oncosis. It was therefore proposed that NDRG2 was not only a biomarker, but also a tumor suppressor for bladder cancer.
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Guangxiu
authors.initials: G
authors.lastname: Wang
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Yingxian
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Minshan
authors.initials: M
authors.lastname: Cai
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, P.R. China.
authors.forename: Yaozhang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009997:Osmotic Pressure; D059807:S Phase Cell Cycle Checkpoints; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
chemical_list: C466228:NDRG2 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D049452:Green Fluorescent Proteins