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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2015 Volume 10 Issue 4

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
October-2015 Volume 10 Issue 4

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

Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells

  • Authors:
    • Suxia Li
    • Suxiu Chen
    • Yiyan Jiang
    • Jiefan Liu
    • Xiaolei Yang
    • Shichao Quan
  • View Affiliations / Copyright

    Affiliations: Department of Tumor Rehabilitation, First Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China
  • Pages: 2652-2656
    |
    Published online on: August 6, 2015
       https://doi.org/10.3892/ol.2015.3577
  • 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

With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‑TKIs) in patients with advanced non‑small cell lung cancer (NSCLC), acquired resistance has become a major clinical problem. A combination of different signaling pathway inhibitors is a promising strategy to overcome this. In the present study, the mitogen‑activated protein kinase kinase 1/2 inhibitor, AZD6244, was used in combination with gefitinib to investigate the efficacy of this treatment in NSCLC cell lines, particularly in gefitinib‑resistant cells. The EGFR‑TKI‑sensitive PC‑9 (mutant EGFR/wild‑type K‑Ras) and EGFR‑TKI‑resistant A549 (wild‑type EGFR/mutant K‑Ras) human NSCLC cell lines were treated with AZD6244 alone, gefitinib alone or the combination of the two drugs, and the effects were evaluated using cell proliferation assays, with alterations in signaling pathways analyzed by western blotting. It was found that the growth inhibitory effect of combination treatment with gefitinib and AZD6244 was greater than that of gefitinib alone in the EGFR‑TKI‑resistant A549 cells. Treatment of A549 cells with gefitinib alone reduced the expression level of the activated form of Akt, and the combination of the two drugs showed stronger inhibition of phosphorylated‑Akt and phosphorylated‑extracellular signal‑regulated kinases. The data showed that the combination of AZD6244 and gefitinib exhibited dose‑dependent synergism in gefitinib‑resistant NSCLC cells. Thus, a preclinical rationale exists for the use of AZD6244 to enhance the efficacy of gefitinib in patients with EGFR‑TKI‑resistant NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, et al: Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 361:947–957. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 26:3543–3551. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R and Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 355:2542–2550. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, et al: Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): A multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 12:735–742. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Ono M and Kuwano M: Molecular mechanisms of epidermal growth factor receptor (EGFR) activation and response to gefitinib and other EGFR-targeting drugs. Clin Cancer Res. 12:7242–7251. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Costa DB, Kobayashi S, Tenen DG and Huberman MS: Pooled analysis of the prospective trials of gefitinib monotherapy for EGFR-mutant non-small cell lung cancers. Lung Cancer. 58:95–103. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, Zakowski MF, Kris MG and Varmus H: Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med. 2:e732005. View Article : Google Scholar : PubMed/NCBI

8 

Sos ML, Rode HB, Heynck S, Peifer M, Fischer F, Klüter S, Pawar VG, Reuter C, Heuckmann JM, Weiss J, et al: Chemogenomic profiling provides insights into the limited activity of irreversible EGFR Inhibitors in tumor cells expressing the T790M EGFR resistance mutation. Cancer Res. 70:868–874. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, et al: MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. 316:1039–1043. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Zhang H, Xu Y, Filipovic A, Lit LC, Koo CY, Stebbing J and Giamas G: SILAC-based phosphoproteomics reveals an inhibitory role of KSR1 in p53 transcriptional activity via modulation of DBC1. Br J Cancer. 109:2675–2684. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Li J, Pan YY and Zhang Y: Synergistic interaction between sorafenib and gemcitabine in EGFR-TKI-sensitive and EGFR-TKI-resistant human lung cancer cell lines. Oncol Lett. 5:440–446. 2013.PubMed/NCBI

12 

Kim KB, Kefford R, Pavlick AC, Infante JR, Ribas A, Sosman JA, Fecher LA, Millward M, McArthur GA, Hwu P, et al: Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol. 31:482–489. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Metro G, Chiari R, Baldi A, De Angelis V, Minotti V and Crinò L: Selumetinib: A promising pharmacologic approach for KRAS-mutant advanced non-small-cell lung cancer. Future Oncol. 9:167–177. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Meloche S and Pouysségur J: The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition. Oncogene. 26:3227–3239. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Balmanno K and Cook SJ: Tumour cell survival signalling by the ERK1/2 pathway. Cell Death Differ. 16:368–377. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Bodoky G, Timcheva C, Spigel DR, La Stella PJ, Ciuleanu TE, Pover G and Tebbutt NC: A phase II open-label randomized study to assess the efficacy and safety of selumetinib (AZD6244 [ARRY-142886]) versus capecitabine in patients with advanced or metastatic pancreatic cancer who have failed first-line gemcitabine therapy. Invest New Drugs. 30:1216–1223. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Hainsworth JD, Cebotaru CL, Kanarev V, Ciuleanu TE, Damyanov D, Stella P, Ganchev H, Pover G, Morris C and Tzekova V: A phase II, open-label, randomized study to assess the efficacy and safety of AZD6244 (ARRY-142886) versus pemetrexed in patients with non-small cell lung cancer who have failed one or two prior chemotherapeutic regimens. J Thorac Oncol. 5:1630–1636. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Kim EY, Kim A, Kim SK and Chang YS: AZD6244 inhibits cisplatin-induced ERK1/2 activation and potentiates cisplatin-associated cytotoxicity in K-ras G12D preclinical models. Cancer Lett. 358:85–91. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li S, Chen S, Jiang Y, Liu J, Yang X and Quan S: Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncol Lett 10: 2652-2656, 2015.
APA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., & Quan, S. (2015). Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncology Letters, 10, 2652-2656. https://doi.org/10.3892/ol.2015.3577
MLA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10.4 (2015): 2652-2656.
Chicago
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10, no. 4 (2015): 2652-2656. https://doi.org/10.3892/ol.2015.3577
Copy and paste a formatted citation
x
Spandidos Publications style
Li S, Chen S, Jiang Y, Liu J, Yang X and Quan S: Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncol Lett 10: 2652-2656, 2015.
APA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., & Quan, S. (2015). Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells. Oncology Letters, 10, 2652-2656. https://doi.org/10.3892/ol.2015.3577
MLA
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10.4 (2015): 2652-2656.
Chicago
Li, S., Chen, S., Jiang, Y., Liu, J., Yang, X., Quan, S."Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells". Oncology Letters 10, no. 4 (2015): 2652-2656. https://doi.org/10.3892/ol.2015.3577
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