酸性环境诱导肝癌HepG2细胞EMT

doi:10.11904/j.issn.1002-3070.2017.03.002

Abstract

Abstract: Objective The objective of this study was to investigate the effect of acidic conditions on epithelial mesenchymal transition(EMT)of HepG2 cells.Methods HepG2 cells were cultured under acidic and alkaline conditions to observe the difference of cell morphology.Wound healing assays were performed to detect the migration ability of the two groups.Matrigel invasion assays were used to detect the invasive ability of the cells.The expression of EMT-related genes at mRNA level was detected by RT-PCR.The expression level of EMT-related gene protein was detected by Western blot.Results The morphology of HepG2 cells was changed from epithelium to interstitial type under acid conditions.The migration ability of HepG2 cells under acidic condition was stronger than that of alkaline conditions.The number of HepG2 cells crossing Matrigel was higher than that of alkaline condition.The mRNA expression of Vimentin,Slug,Snail and Zeb1 related to EMT and the protein expression of Vimentin and MMP9 related to EMT in HepG2 cells were significantly higher than those under alkaline condition.Conclusion The acid conditions can induce the occurrence of EMT in HepG2 cells.

Key words: Acid conditions, Epithelial mesenchymal transition, Hepatocellular carcinoma, HepG2

CLC Number:

R735.7

ZHOU Chunfang,ZHAO Shanshan,SUN Zequn,WU Jun,ZHA Huolong,YUAN Yahong. Acid conditions induces EMT of hepatocellular carcinoma HepG2 cells[J]. PRACTICAL ONCOLOGY JOURNAL, 2017, 31(3): 199-204.

References

1 El-Serag HB.Hepatocellular carcinoma[J].N Engl J Med,2011,365(12):1118-1127.
2 Beach JR,Hussey GS,Miller TE,et al.Myosin II isoform switching mediates invasiveness after TGF-beta-induced epithelial-mesen chymal transition[J].Proc Natl Acad Sci U S A,2011,108(44):17991-17996.
3 Nieto MA.The ins and outs of the epithelial to mesenchymal transition in health and disease[J].Annu Rev Cell Dev Biol,2011,27:347-376.
4 Van Zijl F,Zulehner G,Petz M,et al.Epithelial-mesenchymal transition in hepatocellular carcinoma[J].Future Oncol,2009,5(8):1169-1179.
5 Wang B,Xia YJ,Wei Y,et al.Regulation of side population cells by TGF-β1-induced epithelial-mesenchymal transition in hepatocellular carcinoma cell lines SMMC-7721 and HepG2[J].World Chinese Journal of Digestology,2010,18(23):2416-2421.
6 Wang QJ,Sun S,Li HD,et al.Effect of hepatocellular growth factor on the invasion and metastasis of hepatocellular carcinoma[J].World Chinese Journal of Digestology,2008,16(28):3152-3156.
7 Fu J,Chen Y,Cao J,et al.p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1alpha pathways[J].Hepatology,2011,53(1):181-192.
8 Julien S,Puig I,Caretti E,et al.Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition[J].Oncogene,2007,26(53):7445-7456.
9 Qi MH.Signal pathways associated with epithelial-mesenchymal transition in metastasis of primary hepatocelluar carcinoma[J].World Chinese Journal of Digestology,2012,20(11):953-958.
10 Leong KG,Niessen K,Kulic I,et al.Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin[J].Exp Med,2007,204(12):2935-2948.
11 Whittaker S,Marais R,Zhu AX.The role of signaling pathways in the development and treatment of hepatocellular carcinoma[J].Oncogene,2010,29(36):4989-5005.
12 侍晓辰,张卫东.低氧对肝癌细胞上皮间质转化及侵袭转移能力的影响[J].中国普通外科杂志,2012,21(7):816-820.
13 Andersen AP,Moreira JM,Pedersen SF.Interactions of ion transporters and channels with cancer cell metabolism and the tumour microenvironment[J].Philos Trans R Soc Lond B Biol Sci,2014,369(1638):20130098.
14 Lugini L,Matarrese P,Tinari A,et al.Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells[J].Cancer Res,2006,66(7):3629-3638.
15 Favaro E,Nardo G,Persano L,et al.Hypoxia inducible factor-1α inactivation unveils a link between tumor cell metabolism and hypoxia-induced cell death[J].The American Journal of Pathology,2008,173(4):1186-1201.
16 Gatenby RA,Gawlinski ET,Gmitro AF,et al.Acid-mediated tumor invasion:a multidisciplinary study[J].Cancer Research,2006,66(10):5216-5223.
17 Fukumura D,Jain RK.Tumor microvasculature and microenvironment:targets for anti-angiogenesis and normalization[J].Microvascular Research,2007,74(2):72-84.
18 Winum JY,Rami M,Scozzafava A,et al.Carbonic anhydrase IX:a new druggable target for the design of antitumor agents[J].Medicinal Research Reviews,2008,28(3):445-463.
19 You H,Jin J,Shu H,et al.Small interfering RNA targeting the subunit ATP6L of proton pump V-ATPase overcomes chemoresistance of breast cancer cells[J].Cancer Letters,2009,280(1):110-119.
20 Suzuki A,Maeda T,Baba Y,et al.Acidic extracellular pH promotes epithelial mesenchymal transition in Lewis lung carcinoma model[J].Cancer Cell Int,2014,14(1):129.

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Acid conditions induces EMT of hepatocellular carcinoma HepG2 cells

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