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| Fumonisin B1 promoted HepG2 cell proliferation by upregulating TGF-β signaling pathway |
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ZENG Tian-tian, LU Xiao-dong, CHEN Lu-fang, CHEN Yuan-yuan, SHAO Qi-xiang |
| （School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang Jiangsu 212003, China) |
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Abstract Objective: To investigate the influence of Fumonisin B1(FB1) on the proliferation of HepG2 cells and its possible mechanism.Methods: HepG2 cells were cultured 48 h in prepared DMEM with different concentrations of 0.5, 1.0,10, 50 μmol/L FB1, the morphology of each group were observed under inverted microscope. Cell proliferation was evaluated by Cell Counting Kit 8(CCK-8)assay. The mRNA expression levels of transforming growth factor-β1（TGF-β1), Drosophila mothers against decapentaplegic 4(Smad4) and plasminogen activator inhibitor-1(PAI-1) were detected by quantitative real-timePCR. Results: Microscope showed that cell division was increased in parallel with the increase of FB1 concentration. CCK-8 assay revealed that cell proliferation was remarkably increased after treatment of FB1. In the 0.5 and 1.0 μmol/L groups, mRNA expression of Smad4 and PAI-1 in HepG2 cells showed no significant difference compared with control group, while in the 10 and 50 μmol/L groups were increased dramatically. Conclusion: FB1 could promote cell proliferation effectively, and the elevated level of TGF-β1, Smad4 and PAI-1 in TGF-β pathway may be one of mechanisms for promoting cell proliferation in HepG2 cells.
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Received: 07 January 2014
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| ［1］Gelderblom WC, Jaskiewicz K, Marasas WF,et al. Fumonisins—novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme\[J\]. Appl Environ Microbiol, 1988, 54(7):1806-1811.［2］Alizadeh AM, Rohandel G, Roudbarmohammadi S, et al. Fumonisin B1 contamination of cereals and risk of esophageal cancer in a high risk area in northeastern Iran\[J\]. Asian Pac J Cancer Prev,2012,13(6):2625-2628.［3］Persson EC, Sewram V, Evans AA, et al. Fumonisin B1 and risk of hepatocellular carcinoma in two Chinese cohorts\[J\]. Food Chem Toxicol,2012,50(3/4):679-683.［4］Mullen TD, Jenkins RW, Clarke CJ, et al. Ceramide synthasedependent ceramide generation and programmed cell death: involvement of salvage pathway in regulating postmitochondrial events\[J\]. J Biol Chem, 2011, 286(18):15929-15942.［5］Igarashi D, Bethke G, Xu Y, et al. Patterntriggered immunity suppresses programmed cell death triggered by fumonisin b1\[J\]. PLoS One, 2013, 8(4):e60769.［6］Halasiddappa LM, Koefeler H, Futerman AH, et al. Oxidized phospholipids induce ceramide accumulation in RAW 264.7 macrophages: role of ceramide synthases\[J\]. PLoS One, 2013, 8(7):e70002.［7］Marasas WF, Jaskiewicz K, Venter FS, et al. Fusarium moniliforme contamination of maize in oesophageal cancer areas in Transkei\[J\]. S Afr Med J, 1988, 74(3):110-114.［8］Yoshinari T, Tanaka T, Ishikuro E, et al. Interlaboratory study of an LC-MS/MS method for simultaneous determination of fumonisin B1, B2 and B3 in corn\[J\]. Shokuhin Eiseigaku Zasshi, 2013, 54(4):266-276.［9］Gelineauvan Waes J, Starr L, Maddox J,et al. Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model\[J\]. Birth Defects Res A Clin Mol Teratol, 2005, 73(7):487-497.［10］Gelderblom WC, Abel S, Smuts CM, et al. Fumonisininduced hepatocarcinogenesis: mechanisms related to cancer initiation and promotion\[J\]. Environ Health Perspect, 2001, 109 （Suppl2）:291-300.［11］Merrill AH Jr., van Echten G, Wang E,et al. Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ\[J\]. J Biol Chem, 1993, 268(36):27299-27306.［12］Humpf HU, Schmelz EM, Meredith FI, et al. Acylation of naturally occurring and synthetic 1deoxysphinganines by ceramide synthase. Formation of Npalmitoylaminopentol produces a toxic metabolite of hydrolyzed fumonisin, AP1, and a new category of ceramide synthase inhibitor\[J\].J Biol Chem， 1998,273(30):19060-19064.［13］唐宁，金洁，邓云，等.人源性长寿保障基因2通过与V-ATPase作用抑制肝癌细胞的生长\[J\].生理学报，2010, 62(3):196-202.［14］Chung Y, Fu E. Crosstalk between Shh and TGF-β signaling in cyclosporineenhanced cell proliferation in human gingival fibroblasts\[J\]. PLoS One, 2013, 8(7):e70128.［15］Yin LM, Jiang HF, Wang X, et al. Effects of sodium copper chlorophyllin on mesenchymal stem cell function in aplastic anemia mice\[J\]. Chin J Integr Med, 2013, 19(5):360-366.［16］Liu R, Li J, Teng Z, et al. Overexpressed microRNA-182 promotes proliferation and invasion in prostate cancer PC3 cells by downregulating Nmyc downstream regulated gene 1 (NDRG1)\[J\]. PLoS One, 2013, 8(7):e68982.［17］Zotes TM, Arias CF, Fuster JJ, et al. PI3K p110γ deletion attenuates murine atherosclerosis by reducing macrophage proliferation but not polarization or apoptosis in lesions\[J\]. PLoS One, 2013, 8(8):e72674.［18］Dzieran J, Fabian J, Feng T, et al. Comparative analysis of TGF-β/Smad signaling dependent cytostasis in human hepatocellular carcinoma cell lines\[J\]. PLoS One, 2013, 8(8):e72252.［19］Halder SK, Beauchamp RD, Datta PK. A specific inhibitor of TGF-β receptor kinase, SB-431542, as a potent antitumor agent for human cancers\[J\]. Neoplasia, 2005, 7(5):509-521.［20］Zhang L, Zhou F, Ten Dijke P. Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer\[J\]. Trends Biochem Sci, 2013, 38(12):612-620.［21］Katz LH, Li Y, Chen JS, et al. Targeting TGFβ signaling in cancer\[J\]. Expert Opin Ther Targets, 2013, 17(7):743-760.［22］Matsubara T, Tanaka N, Patterson AD, et al. Lithocholic acid disrupts phospholipid and sphingolipid homeostasis leading to cholestasis in mice\[J\]. Hepatology, 2011, 53(4):1282-1293. |
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2014, Vol. 24 
