Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
September-2019 Volume 18 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2019 Volume 18 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition

  • Authors:
    • Jianyun Zheng
    • Jianxin Yu
    • Min Yang
    • Li Tang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, The First Affiliated Hospital of Xi'an Medical University, School of General Medicine, Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China, Department of Laboratory, Central Hospital of Shanxian County, Heze, Shandong 274399, P.R. China, Department of Gynaecology and Obstetrics, Puyang Oil Field General Hospital, Puyang, Henan 457001, P.R. China
  • Pages: 1823-1830
    |
    Published online on: July 9, 2019
       https://doi.org/10.3892/etm.2019.7754
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cervical cancer (CC) is the second most common malignant cancer among women. Gefitinib was one of the first‑generation epidermal growth factor receptor‑tyrosine kinase inhibitors in clinical trials. However, the underlying mechanism of gefitinib in regulating CC progression remains unknown. In the current study, two CC cell lines, HeLa and Siha, were used to investigate the effects of gefitinib. Cell counting kit‑8 assays demonstrated that treatment with gefitinib exerted strong cytotoxicity in HeLa and Siha cells. Flow cytometry was used to examine cell cycle progression and apoptosis. Treatment with gefitinib enhanced the number of cells in the G0/G1 phase and increased apoptosis in HeLa and Siha cells. Furthermore, treatment with gefitinib decreased the protein expression level of Bcl‑2 and increased the protein expression level of Bax. Taken together, these results suggest that gefitinib may suppress CC cell proliferation and induce cell cycle arrest and apoptosis. The current study also demonstrated that treatment with gefitinib suppressed epithelial‑mesenchymal transition (EMT) as the expression level of the epithelial marker, E‑cadherin was increased, while the expression level of the mesenchymal marker, vimentin was decreased. The current study demonstrated that treatment with gefitinib decreased the protein expression levels of phosphorylated‑GSK3β and β‑catenin, which suggests that gefitinib may be a potential novel therapeutic strategy in CC by suppressing the Wnt/β‑catenin signaling pathway and EMT to inhibit tumor metastasis in CC cells. In conclusion, gefitinib may suppress the EMT process during cell invasion and induce cell apoptosis and cell cycle arrest via inhibition of the Wnt/β‑catenin signaling pathway.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Zhang R, Lu H, Lyu YY, Yang XM, Zhu LY, Yang GD, Jiang PC, Re Y, Song WW, Wang JH, et al: E6/E7-P53-POU2F1-CTHRC1 axis promotes cervical cancer metastasis and activates Wnt/PCP pathway. Sci Rep. 7:447442017. View Article : Google Scholar : PubMed/NCBI

2 

Bahrami A, Hasanzadeh M, ShahidSales S, Yousefi Z, Kadkhodayan S, Farazestanian M, Joudi Mashhad M, Gharib M, Mahdi Hassanian S and Avan A: Clinical significance and prognosis value of Wnt signaling pathway in cervical cancer. J Cell Biochem. 118:3028–3033. 2017. View Article : Google Scholar : PubMed/NCBI

3 

Chung MT, Lai HC, Sytwu HK, Yan MD, Shih YL, Chang CC, Yu MH, Liu HS, Chu DW and Lin YW: SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway. Gynecol Oncol. 112:646–653. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Cui N, Yang WT and Zheng PS: Slug inhibits the proliferation and tumor formation of human cervical cancer cells by up- regulating the p21/p27 proteins and down-regulating the activity of the Wnt/β-catenin signaling pathway via the trans-suppression Akt1/p-Akt1 expression. Oncotarget. 7:26152–26167. 2016. View Article : Google Scholar : PubMed/NCBI

5 

Hua F, Liu S, Zhu L, Ma N, Jiang S and Yang J: Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through Wnt/beta-catenin signaling pathway in cervical cancer. Biomed Pharmacother. 92:1128–1134. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Kloth JN, Fleuren GJ, Oosting J, de Menezes RX, Eilers PH, Kenter GG and Gorter A: Substantial changes in gene expression of Wnt, MAPK and TNFalpha pathways induced by TGF-beta1 in cervical cancer cell lines. Carcinogenesis. 26:1493–1502. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Kwan HT, Chan DW, Cai PC, Mak CS, Yung MM, Leung TH, Wong OG, Cheung AN and Ngan HY: AMPK activators suppress cervical cancer cell growth through inhibition of DVL3 mediated Wnt/beta-catenin signaling activity. PLoS One. 8:e535972013. View Article : Google Scholar : PubMed/NCBI

8 

Lan K, Zhao Y, Fan Y, Ma B, Yang S, Liu Q, Linghu H and Wang H: Sulfiredoxin may promote cervical cancer metastasis via Wnt/β-catenin signaling pathway. Int J Mol Sci. 18:E9172017. View Article : Google Scholar : PubMed/NCBI

9 

Lee J, Yoon YS and Chung JH: Epigenetic silencing of the WNT antagonist DICKKOPF-1 in cervical cancer cell lines. Gynecol Oncol. 109:270–274. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Li F, Wang T and Tang S: SOX14 promotes proliferation and invasion of cervical cancer cells through Wnt/β-catenin pathway. Int J Clin Exp Pathol. 8:1698–1704. 2015.PubMed/NCBI

11 

Xu CR, Zhong WZ, Zhou Q, Zhang XC, Yang JJ and Wu YL: Heterogeneity of the resistance to gefitinib treatment in a non-small cell lung cancer patient with active epidermal growth factor receptor mutation. Thorac Cancer. 8:51–53. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Yang RF, Yu B, Zhang RQ, Wang XH, Li C, Wang P, Zhang Y, Han B, Gao XX, Zhang L and Jiang ZM: Bevacizumab and gefitinib enhanced whole-brain radiation therapy for brain metastases due to non-small-cell lung cancer. Braz J Med Biol Res. 51:e60732017. View Article : Google Scholar : PubMed/NCBI

13 

Yang XB, Chai XS, Wu WY, Long SQ, Deng H, Pan ZQ, He WF, Zhou YS, Liao GY and Xiao SJ: Gefitinib plus Fuzheng Kang'ai formula () in patients with advanced non-small cell lung cancer with epidermal growth factor receptor mutation: A randomized controlled trial. Chin J Integr Med. 24:734–740. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Yang Z, Hackshaw A, Feng Q, Fu X, Zhang Y, Mao C and Tang J: Comparison of gefitinib, erlotinib and afatinib in non-small cell lung cancer: A meta-analysis. Int J Cancer. 140:2805–2819. 2017. View Article : Google Scholar : PubMed/NCBI

15 

Xu S and Gotlieb AI: Wnt3a/β-catenin increases proliferation in heart valve interstitial cells. Cardiovasc Pathol. 22:156–166. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Qureshi R, Arora H and Rizvi MA: EMT in cervical cancer: Its role in tumour progression and response to therapy. Cancer Lett. 356:321–331. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Xu S, Fan Y, Li D, Liu Y and Chen X: Glycoprotein nonmetastatic melanoma protein B accelerates tumorigenesis of cervical cancer in vitro by regulating the Wnt/β-catenin pathway. Braz J Med Biol Res. 52:e75672018. View Article : Google Scholar : PubMed/NCBI

18 

Li S, Yang F, Wang M, Cao W and Yang Z: miR-378 functions as an onco-miRNA by targeting the ST7L/Wnt/β-catenin pathway in cervical cancer. Int J Mol Med. 40:1047–1056. 2017. View Article : Google Scholar : PubMed/NCBI

19 

Liu P, Ma S, Liu H, Han H and Wang S: HCFU inhibits cervical cancer cells growth and metastasis by inactivating Wnt/β-catenin pathway. J Cell Biochem. Dec 12–2017.(Epub ahead of print) doi: 10.1002/jcb.26570.

20 

Liu XF, Li XY, Zheng PS and Yang WT: DAX1 promotes cervical cancer cell growth and tumorigenicity through activation of Wnt/β-catenin pathway via GSK3beta. Cell Death Dis. 9:3392018. View Article : Google Scholar : PubMed/NCBI

21 

Hartmann S, Neckel N, Seher A, Mutzbauer G, Brands RC, Linz C, Kübler AC and Müller-Richter UD: Erlotinib and gefitinib responsiveness in head and neck cancer cell lines-a comparing analysis with cetuximab. Clin Oral Investig. 20:759–769. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Li Q, Zhang D, Chen X, He L, Li T, Xu X and Li M: Nuclear PKM2 contributes to gefitinib resistance via upregulation of STAT3 activation in colorectal cancer. Sci Rep. 5:160822015. View Article : Google Scholar : PubMed/NCBI

23 

Geng D, Sun D, Zhang L and Zhang W: The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine. Afr Health Sci. 15:594–597. 2015. View Article : Google Scholar : PubMed/NCBI

24 

Jiang C, Xu R, Li XX, Wang YY, Liang WQ, Zeng JD, Zhang SS, Xu XY, Yang Y, Zhang MY, et al: p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis. Cell Cycle. 16:1673–1682. 2017. View Article : Google Scholar : PubMed/NCBI

25 

Fernando G, Paul F, Laura J, Alejandra AM, Gabriela M and Alberto PL: Is the Wnt/β catenin signalling pathway activated in Seminoma? An immunohistochemical study. J Cancer Res Ther. 12:1075–1079. 2016. View Article : Google Scholar : PubMed/NCBI

26 

Yang C, Du W and Yang D: Inhibition of green tea polyphenol EGCG((−)-epigallocatechin-3-gallate) on the proliferation of gastric cancer cells by suppressing canonical wnt/β-catenin signalling pathway. Int J Food Sci Nutr. 67:818–827. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Mittag S, Valenta T, Weiske J, Bloch L, Klingel S, Gradl D, Wetzel F, Chen Y, Petersen I, Basler K and Huber O: A novel role for the tumour suppressor Nitrilase1 modulating the Wnt/β-catenin signalling pathway. Cell Discov. 2:150392016. View Article : Google Scholar : PubMed/NCBI

28 

van Zuylen WJ, Rawlinson WD and Ford CE: The Wnt pathway: A key network in cell signalling dysregulated by viruses. Rev Med Virol. 26:340–355. 2016. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zheng J, Yu J, Yang M and Tang L: Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition. Exp Ther Med 18: 1823-1830, 2019.
APA
Zheng, J., Yu, J., Yang, M., & Tang, L. (2019). Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition. Experimental and Therapeutic Medicine, 18, 1823-1830. https://doi.org/10.3892/etm.2019.7754
MLA
Zheng, J., Yu, J., Yang, M., Tang, L."Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition". Experimental and Therapeutic Medicine 18.3 (2019): 1823-1830.
Chicago
Zheng, J., Yu, J., Yang, M., Tang, L."Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1823-1830. https://doi.org/10.3892/etm.2019.7754
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng J, Yu J, Yang M and Tang L: Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition. Exp Ther Med 18: 1823-1830, 2019.
APA
Zheng, J., Yu, J., Yang, M., & Tang, L. (2019). Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition. Experimental and Therapeutic Medicine, 18, 1823-1830. https://doi.org/10.3892/etm.2019.7754
MLA
Zheng, J., Yu, J., Yang, M., Tang, L."Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition". Experimental and Therapeutic Medicine 18.3 (2019): 1823-1830.
Chicago
Zheng, J., Yu, J., Yang, M., Tang, L."Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition". Experimental and Therapeutic Medicine 18, no. 3 (2019): 1823-1830. https://doi.org/10.3892/etm.2019.7754
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team