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Article

Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis

  • Authors:
    • Wei Li
    • Lei Cao
    • Liang Han
    • Qinhong Xu
    • Qingyong Ma
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, P.R. China, Department of Pharmacology, College of Medicine, Xi'an Jiaotong University, Xi'an 710061, P.R. China
  • Pages: 2613-2620
    |
    Published online on: March 27, 2015
       https://doi.org/10.3892/ijo.2015.2938
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Abstract

Our previous study revealed that superoxide dismutase (SOD)-dependent production of reactive oxygen species (ROS) was able to increase the invasive ability of pancreatic cancer cells. However, the underlying mechanisms by which SOD enhances metastasis are still not fully elucidated. As epithelial-mesenchymal transition (EMT) is a key player in tumor metastasis, the aim of this study was to evaluate whether SOD affects EMT in pancreatic cancer cells and the related mechanism. Human pancreatic cancer cells BxPC-3 and Panc-1 were utilized to examine the level of hydrogen peroxide (H2O) in the absence or presence of SOD and catalase (CAT). The activation of phospho-ERK and phospho-NF-κB were measured by western blot analysis. Wound healing assay and transwell invasion assay were used to detect the migratory and invasive potential of cancer cells. The EMT-related factors, E-cadherin, N-cadherin and vimentin were detected by QT-PCR and western blot analysis. The results of present study showed that SOD not only increased cell migration and invasion in pancreatic cancer, but also mediated the expression of EMT-related factors and cell morphology. In addition, the levels of phospho-ERK and phospho-NF-κB were induced by SOD which could be counter-balanced by both CAT treatment and PD 98059 (an ERK inhibitor). Taken together, these data indicate that SOD promotes the invasive and migratory activity of pancreatic cancer. Blocking the H2O2/ERK/NF-κB axis might be a novel strategy for the treatment of this severe malignancy.
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View References

1 

Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Sarkar FH, Banerjee S and Li Y: Pancreatic cancer: Pathogenesis, prevention and treatment. Toxicol Appl Pharmacol. 224:326–336. 2007. View Article : Google Scholar

3 

Castellanos EH, Cardin DB and Berlin JD: Treatment of early-stage pancreatic cancer. Oncology (Williston Park). 25:182–189. 2011.

4 

Li W, Ma Q, Li J, Guo K, Liu H, Han L and Ma G: Hyperglycemia enhances the invasive and migratory activity of pancreatic cancer cells via hydrogen peroxide. Oncol Rep. 25:1279–1287. 2011.PubMed/NCBI

5 

Lee DJ and Kang SW: Reactive oxygen species and tumor metastasis. Mol Cells. 35:93–98. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Li W, Ma Q, Liu J, Han L, Ma G, Liu H, Shan T, Xie K and Wu E: Hyperglycemia as a mechanism of pancreatic cancer metastasis. Front Biosci (Landmark Ed). 17:1761–1774. 2012. View Article : Google Scholar

7 

Costa A, Scholer-Dahirel A and Mechta-Grigoriou F: The role of reactive oxygen species and metabolism on cancer cells and their microenvironment. Semin Cancer Biol. 25:23–32. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Liu Z, Li S, Cai Y, Wang A, He Q, Zheng C, Zhao T, Ding X and Zhou X: Manganese superoxide dismutase induces migration and invasion of tongue squamous cell carcinoma via H2O2-dependent Snail signaling. Free Radic Biol Med. 53:44–50. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Lewis A, Du J, Liu J, Ritchie JM, Oberley LW and Cullen JJ: Metastatic progression of pancreatic cancer: Changes in antioxidant enzymes and cell growth. Clin Exp Metastasis. 22:523–532. 2005. View Article : Google Scholar

10 

Duan W, Li R, Ma J, Lei J, Xu Q, Jiang Z, Nan L, Li X, Wang Z, Huo X, et al: Overexpression of Nodal induces a metastatic phenotype in pancreatic cancer cells via the Smad2/3 pathway. Oncotarget. 6:1490–1506. 2015.PubMed/NCBI

11 

Inumaru J, Nagano O, Takahashi E, Ishimoto T, Nakamura S, Suzuki Y, Niwa S, Umezawa K, Tanihara H and Saya H: Molecular mechanisms regulating dissociation of cell-cell junction of epithelial cells by oxidative stress. Genes Cells. 14:703–716. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Barnett P, Arnold RS, Mezencev R, Chung LW, Zayzafoon M and Odero-Marah V: Snail-mediated regulation of reactive oxygen species in ARCaP human prostate cancer cells. Biochem Biophys Res Commun. 404:34–39. 2011. View Article : Google Scholar :

13 

Das TP, Suman S and Damodaran C: Induction of reactive oxygen species generation inhibits epithelial-mesenchymal transition and promotes growth arrest in prostate cancer cells. Mol Carcinog. 53:537–547. 2014. View Article : Google Scholar

14 

Cho KH, Choi MJ, Jeong KJ, Kim JJ, Hwang MH, Shin SC, Park CG and Lee HY: A ROS/STAT3/HIF-1α signaling cascade mediates EGF-induced TWIST1 expression and prostate cancer cell invasion. Prostate. 74:528–536. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Wu WS, Wu JR and Hu CT: Signal cross talks for sustained MAPK activation and cell migration: The potential role of reactive oxygen species. Cancer Metastasis Rev. 27:303–314. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

17 

Li F, Wang H, Huang C, Lin J, Zhu G, Hu R and Feng H: Hydrogen peroxide contributes to the manganese superoxide dismutase promotion of migration and invasion in glioma cells. Free Radic Res. 45:1154–1161. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Hsieh HL, Wang HH, Wu WB, Chu PJ and Yang CM: Transforming growth factor-β1 induces matrix metalloproteinase-9 and cell migration in astrocytes: Roles of ROS-dependent ERK- and JNK-NF-κB pathways. J Neuroinflammation. 7:882010. View Article : Google Scholar

19 

Wu Y and Zhou BP: New insights of epithelial-mesenchymal transition in cancer metastasis. Acta Biochim Biophys Sin (Shanghai). 40:643–650. 2008. View Article : Google Scholar

20 

Wray CJ, Ahmad SA, Matthews JB and Lowy AM: Surgery for pancreatic cancer: Recent controversies and current practice. Gastroenterology. 128:1626–1641. 2005. View Article : Google Scholar : PubMed/NCBI

21 

Iwatsuki M, Mimori K, Yokobori T, Ishi H, Beppu T, Nakamori S, Baba H and Mori M: Epithelial-mesenchymal transition in cancer development and its clinical significance. Cancer Sci. 101:293–299. 2010. View Article : Google Scholar

22 

Chiu WT, Shen SC, Chow JM, Lin CW, Shia LT and Chen YC: Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE(2) activation. Neurobiol Dis. 37:118–129. 2010. View Article : Google Scholar

23 

Chaiswing L, Zhong W, Cullen JJ, Oberley LW and Oberley TD: Extracellular redox state regulates features associated with prostate cancer cell invasion. Cancer Res. 68:5820–5826. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Hempel N, Carrico PM and Melendez JA: Manganese super-oxide dismutase (Sod2) and redox-control of signaling events that drive metastasis. Anticancer Agents Med Chem. 11:191–201. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Chen PM, Wu TC, Wang YC, Cheng YW, Sheu GT, Chen CY and Lee H: Activation of NF-κB by SOD2 promotes the aggressiveness of lung adenocarcinoma by modulating NKX2-1-mediated IKKβ expression. Carcinogenesis. 34:2655–2663. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Kinnula VL and Crapo JD: Superoxide dismutases in malignant cells and human tumors. Free Radic Biol Med. 36:718–744. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Toh Y, Kuninaka S, Oshiro T, Ikeda Y, Nakashima H, Baba H, Kohnoe S, Okamura T, Mori M and Sugimachi K: Overexpression of manganese superoxide dismutase mRNA may correlate with aggressiveness in gastric and colorectal adenocarcinomas. Int J Oncol. 17:107–112. 2000.PubMed/NCBI

28 

Wang S, Wang F, Shi X, Dai J, Peng Y, Guo X, Wang X, Shen H and Hu Z: Association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and cancer risk - A meta-analysis. Eur J Cancer. 45:2874–2881. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Tang H, Dong X, Day RS, Hassan MM and Li D: Antioxidant genes, diabetes and dietary antioxidants in association with risk of pancreatic cancer. Carcinogenesis. 31:607–613. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Connor KM, Hempel N, Nelson KK, Dabiri G, Gamarra A, Belarmino J, Van De Water L, Mian BM and Melendez JA: Manganese superoxide dismutase enhances the invasive and migratory activity of tumor cells. Cancer Res. 67:10260–10267. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Mori K, Shibanuma M and Nose K: Invasive potential induced under long-term oxidative stress in mammary epithelial cells. Cancer Res. 64:7464–7472. 2004. View Article : Google Scholar : PubMed/NCBI

32 

Kim MC, Cui FJ and Kim Y: Hydrogen peroxide promotes epithelial to mesenchymal transition and stemness in human malignant mesothelioma cells. Asian Pac J Cancer Prev. 14:3625–3630. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Lee KH, Kim SW and Kim JR: Reactive oxygen species regulate urokinase plasminogen activator expression and cell invasion via mitogen-activated protein kinase pathways after treatment with hepatocyte growth factor in stomach cancer cells. J Exp Clin Cancer Res. 28:732009. View Article : Google Scholar : PubMed/NCBI

34 

Liu J, Ben QW, Yao WY, Zhang JJ, Chen DF, He XY, Li L and Yuan YZ: BMP2 induces PANC-1 cell invasion by MMP-2 over-expression through ROS and ERK. Front Biosci (Landmark Ed). 17:2541–2549. 2012. View Article : Google Scholar

35 

Gilmore TD: Introduction to NF-kappaB: Players, pathways, perspectives. Oncogene. 25:6680–6684. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Li W, Cao L, Han L, Xu Q and Ma Q: Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis. Int J Oncol 46: 2613-2620, 2015.
APA
Li, W., Cao, L., Han, L., Xu, Q., & Ma, Q. (2015). Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis. International Journal of Oncology, 46, 2613-2620. https://doi.org/10.3892/ijo.2015.2938
MLA
Li, W., Cao, L., Han, L., Xu, Q., Ma, Q."Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis". International Journal of Oncology 46.6 (2015): 2613-2620.
Chicago
Li, W., Cao, L., Han, L., Xu, Q., Ma, Q."Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis". International Journal of Oncology 46, no. 6 (2015): 2613-2620. https://doi.org/10.3892/ijo.2015.2938
Copy and paste a formatted citation
x
Spandidos Publications style
Li W, Cao L, Han L, Xu Q and Ma Q: Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis. Int J Oncol 46: 2613-2620, 2015.
APA
Li, W., Cao, L., Han, L., Xu, Q., & Ma, Q. (2015). Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis. International Journal of Oncology, 46, 2613-2620. https://doi.org/10.3892/ijo.2015.2938
MLA
Li, W., Cao, L., Han, L., Xu, Q., Ma, Q."Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis". International Journal of Oncology 46.6 (2015): 2613-2620.
Chicago
Li, W., Cao, L., Han, L., Xu, Q., Ma, Q."Superoxide dismutase promotes the epithelial-mesenchymal transition of pancreatic cancer cells via activation of the H2O2/ERK/NF-κB axis". International Journal of Oncology 46, no. 6 (2015): 2613-2620. https://doi.org/10.3892/ijo.2015.2938
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