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ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins

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Abstract

Small-molecule inhibitors targeted MAPK have been wildly used for some cancer therapeutics as a biologically viable model, but no one has been used for cervical caner. ERK1/2, one of MAPK kinases, is expressed high in cervical cancer tissue. The aim of the present study was to evaluate the effects of ERK1/2 inhibitor U0126 on proliferation and apoptosis of cervical cancer cells and appraise the correlated mechanism of the effects. In this study, the cell proliferation of Hela and C33A cervical cancer cells was tested by Cell Counting Kit-8 (CCK8) assay and cell counting after treated with ERK1/2 inhibitor U0126. The cell cycle and apoptosis were evaluated by flow cytometry (FCM). The protein levels of ERK1/2 and c-Fos and c-Jun were detected by Western blot. The results indicated that after down-regulating ERK1/2 proteins with the inhibitor U0126, Hela and C33A cells proliferation was inhibited, cell apoptosis was promoted, the proportions of G0/G1 stage in cell cycle increased, and G2/M stages decreased. After down-regulating ERK1/2 proteins of Hela and C33A cells, the expression levels of p–c-Fos protein decreased, while p–c-Jun protein increased. The results of this study indicated that ERK1/2 may promote the development of cervical cancer cells, suggesting ERK1/2 inhibitor may be used as an effective target for cervical cancer therapies working for. It might inhibit cervical cancer cells growth via regulating the transcription factors expression of c-Fos and c-Jun.

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References

  1. Zhang B, Zhou AF, Zhu CC, et al. Risk factors for cervical cancer in rural areas of Wuhan China: a matched case-control study. Asian Pac J Cancer Prev. 2013;14:7595–600.

    Article  PubMed  Google Scholar 

  2. Rouzier R. Epidemiology and risk factors for cancer of the uterus. Rev Prat. 2014;64:774–9.

    PubMed  Google Scholar 

  3. Feneyrolles C, Spenlinhauer A, Guiet L, Fauvel B, et al. Axl kinase as a key target for oncology: focus on small molecule inhibitors. Mol Cancer Ther. 2014;13:2141–8.

    Article  CAS  PubMed  Google Scholar 

  4. Smyth EC, Sclafani F, Cunningham D. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors. Onco Targets Ther. 2014;7:1001–14.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Yun JI, Kim HR, Park H, et al. Small molecule inhibitors of the hedgehog signaling pathway for the treatment of cancer. Arch Pharm Res. 2012;35:1317–33.

    Article  CAS  PubMed  Google Scholar 

  6. Tasian SK, Teachey DT, Rheingold SR. Targeting the PI3K/mTOR pathway in pediatric hematologic malignancies. Front Oncol. 2014;4:108.

    PubMed Central  PubMed  Google Scholar 

  7. Miller CR, Oliver KE, Farley JH. MEK1/2 inhibitors in the treatment of gynecologic malignancies. Gynecol Oncol. 2014;133:128–37.

    Article  CAS  PubMed  Google Scholar 

  8. Yoon S, Seger R. The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions. Growth Factors. 2006;24:21–44.

    Article  CAS  PubMed  Google Scholar 

  9. Roskoski R Jr. ERK1/2 MAP kinases: structure, function, and regulation. Pharmacol Res. 2012;66:105–43.

    Article  CAS  PubMed  Google Scholar 

  10. Pan F, Hong LQ. Insulin promotes proliferation and migration of breast cancer cells through the extracellular regulated kinase pathway. Asian Pac J Cancer Prev. 2014;15:6349–52.

    Article  PubMed  Google Scholar 

  11. El-Baba C, Mahadevan V, Fahlbusch FB, et al. Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer. Mol Cancer. 2014;13:201.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Song X, Wang Y, Du H, et al. Overexpression of HepaCAM inhibits cell viability and motility through suppressing nucleus translocation of androgen receptor and ERK signaling in prostate cancer. Prostate. 2014;74:1023–33.

    Article  CAS  PubMed  Google Scholar 

  13. Lu Z, Ding L, Hong H, et al. Claudin-7 inhibits human lung cancer cell migration and invasion through ERK/MAPK signaling pathway. Exp Cell Res. 2011;317:1935–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Deschenes-Simard X, Kottakis F, Meloche S, et al. ERKs in cancer: friends or foes? Cancer Res. 2014;74:412–9.

    Article  CAS  PubMed  Google Scholar 

  15. Cai DH, Wang D, Keefer J, et al. C/EBP alpha: AP-1 leucine zipper heterodimers bind novel DNA elements, activate the PU.1 promoter and direct monocyte lineage commitment more potently than C/EBP alpha homodimers or AP-1. Oncogene. 2008;27:2772–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Shaulian E, Karin M. AP-1 as a regulator of cell life and death. Nat Cell Biol. 2002;4:E131–6.

    Article  CAS  PubMed  Google Scholar 

  17. Manimala NJ, Frost CD, Lane ML, et al. Cardiac hormones target nuclear oncogenes c-Fos and c-Jun in carcinoma cells. Eur J Clin Invest. 2013;43:1156–62.

    CAS  PubMed  Google Scholar 

  18. Santarpia L, Lippman SM, El-Naggar AK. Targeting the MAPK-RAS-RAF signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16:103–19.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Lee EK, Regenold WT, Shapiro P. Inhibition of aldose reductase enhances HeLa cell sensitivity to chemotherapeutic drugs and involves activation of extracellular signal-regulated kinases. Anticancer Drugs. 2002;13:859–68.

    Article  CAS  PubMed  Google Scholar 

  20. Wang X, Govind S, Sajankila SP, et al. Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin. Mol Nutr Food Res. 2011;55:1572–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Lorusso PM, Adjei AA, Varterasian M, et al. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. J Clin Oncol. 2005;23:5281–93.

    Article  CAS  PubMed  Google Scholar 

  22. Rinehart J, Adjei AA, Lorusso PM, et al. Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer. J Clin Oncol. 2004;22:4456–62.

    Article  CAS  PubMed  Google Scholar 

  23. LoRusso PM, Krishnamurthi SS, Rinehart JJ, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral MAPK/ERK kinase inhibitor PD-0325901 in patients with advanced cancers. Clin Cancer Res. 2010;16:1924–37.

    Article  CAS  PubMed  Google Scholar 

  24. Yeh TC, Marsh V, Bernat BA, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res. 2007;13:1576–83.

    Article  CAS  PubMed  Google Scholar 

  25. Marampon F, Gravina GL, Popov VM, et al. Close correlation between MEK/ERK and Aurora-B signaling pathways in sustaining tumorigenic potential and radioresistance of gynecological cancer cell lines. Int J Oncol. 2014;44:285–94.

    CAS  PubMed  Google Scholar 

  26. Hess J, Angel P, Schorpp-Kistner M. AP-1 subunits: quarrel and harmony among siblings. J Cell Sci. 2004;117:5965–73.

    Article  CAS  PubMed  Google Scholar 

  27. Prusty BK, Das BC. Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activity in HeLa cells by curcumin. Int J Cancer. 2005;113:951–60.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This research is supported by the National Natural Science Foundation of China (Grant No. 81273157 and No. 30872166) and the Natural Science Foundation of Shanxi Province, China (Grant No. 2008011075-1).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China

    Lixia Bai, Jintao Wang, Ling Ding, Chenfei Gao, Huijie Kang, Xiao Chen, Xuesong Sun & Juan Xu

  2. Maternal and Children Health Care of Shanxi Province Affiliated to Shanxi Medical University, Taiyuan, 030013, China

    Lixia Bai

  3. Faculty of Arts and Science, University of Toronto, Toronto, Canada

    Rui Mao

  4. Department of Biomedical Science, Mercer University School of Medicine, Macon, GA, USA

    Shiwen Jiang

Authors
  1. Lixia Bai
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  2. Rui Mao
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  3. Jintao Wang
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  4. Ling Ding
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  5. Shiwen Jiang
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  6. Chenfei Gao
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  7. Huijie Kang
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  8. Xiao Chen
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  9. Xuesong Sun
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  10. Juan Xu
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Correspondence to Jintao Wang.

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Bai, L., Mao, R., Wang, J. et al. ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins. Med Oncol 32, 57 (2015). https://doi.org/10.1007/s12032-015-0490-5

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  • DOI: https://doi.org/10.1007/s12032-015-0490-5

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