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
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
August-2014 Volume 45 Issue 2

Full Size Image

Cover Legend PDF

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
August-2014 Volume 45 Issue 2

Full Size Image

Cover Legend PDF

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

Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo

  • Authors:
    • Dan Li
    • Yingli Jin
    • Ying Sun
    • Jing Lei
    • Chaoying Liu
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital of Jilin University, Changchun, Jilin, P.R. China, Department of Pharmacology, College of Basic Medical Science, Jilin University, Changchun, Jilin, P.R. China
  • Pages: 813-821
    |
    Published online on: June 2, 2014
       https://doi.org/10.3892/ijo.2014.2479
  • 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

Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival and metastasis in several types of cancers. However, the expression of TLR4 in patients with non-small cell lung cancer (NSCLC) and its biological function in the development and progression of NSCLC have not been elucidated to date. Here, we sought to characterize the expression of TLR4 in patients with NSCLC and to investigate the biological roles of TLR4 in lung metastasis, cell invasion and survival. In this study, we found that TLR4 expression was elevated in most patients with NSCLC, and its expression levels correlated with key pathological characteristics, including tumor differentiation, stage and metastasis. Our data also showed that downregulation of TLR4 expression using an RNA silencing approach in A549 tumor cells significantly suppressed cell proliferation, cell migration and cell invasion, and induced tumor apoptosis in vitro, and suppressed tumor growth in vivo. In addition, we also found that downregulation of TLR4 expression significantly decreased cell TNF-α and IL-6 levels. Furthermore, we found that knockdown of TLR4 was able to significantly suppress constitutive phosphorylation of Akt and PI3K, which may contribute to the inhibition of tumor growth. These data suggest that TLR4 plays an important role in tumorigenic properties of human NSCLC, and that RNA interference-directed targeting of TLR4 could be used as a potential anticancer therapeutic target in NSCLC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Jemal A, Siegel R, Ward E, Hao Y, Xu J and Thun MJ: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar

2 

Reungwetwattana T, Weroha SJ and Molina JR: Oncogenic pathways, molecularly targeted therapies, and highlighted clinical trials in non-small-cell lung cancer (NSCLC). Clin Lung Cancer. 13:252–266. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Schiller JH: Small cell lung cancer: defining a role for emerging platinum drugs. Oncology. 63:105–114. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Roy M, Luo YH, Ye M and Liu J: Nonsmall cell lung cancer therapy: insight into multitargeted small-molecule growth factor receptor inhibitors. Biomed Res Int. 2013:9647432013.PubMed/NCBI

5 

Medzhitov R, Preston-Hurlburt P and Janeway CA Jr: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 388:394–397. 1997. View Article : Google Scholar

6 

Takeda K, Kaisho T and Akira S: Toll-like receptors. Annu Rev Immunol. 21:335–376. 2003. View Article : Google Scholar

7 

Medzhitov R and Janeway CA Jr: Decoding the patterns of self and nonself by the innate immune system. Science. 296:298–300. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Elson G, Dunn-Siegrist I, Daubeuf B and Pugin J: Contribution of Toll-like receptors to the innate immune response to Gram-negative and Gram-positive bacteria. Blood. 109:1574–1583. 2007. View Article : Google Scholar : PubMed/NCBI

9 

De Bouteiller O, Merck E, Hasan UA, et al: Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH. J Biol Chem. 280:38133–38145. 2005.PubMed/NCBI

10 

Goto Y, Arigami T, Kitago M, et al: Activation of Toll-like receptors 2, 3, and 4 on human melanoma cells induces inflammatory factors. Mol Cancer Ther. 7:3642–3653. 2008. View Article : Google Scholar : PubMed/NCBI

11 

Kelly MG, Alvero AB, Chen R, et al: TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer. Cancer Res. 66:3859–3868. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Fukata M, Chen A, Vamadevan AS, et al: Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology. 133:1869–1881. 2007. View Article : Google Scholar : PubMed/NCBI

13 

O’Neill LA, Bryant CE and Doyle SL: Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 61:177–197. 2009.PubMed/NCBI

14 

Yu L and Chen S: Toll-like receptors expressed in tumor cells: targets for therapy. Cancer Immunol Immunother. 57:1271–1278. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Garza-Gonzalez E, Bosques-Padilla FJ, Mendoza-Ibarra SI, Flores-Gutierrez JP, Maldonado-Garza HJ and Perez-Perez GI: Assessment of the toll-like receptor 4 Asp299Gly, Thr399Ile and interleukin-8 −251 polymorphisms in the risk for the development of distal gastric cancer. BMC Cancer. 7:702007.PubMed/NCBI

16 

Wang JP, Zhang Y, Wei X, et al: Circulating Toll-like receptor (TLR) 2, TLR4, and regulatory T cells in patients with chronic hepatitis C. APMIS. 118:261–270. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Yang H, Zhou H, Feng P, et al: Reduced expression of Toll-like receptor 4 inhibits human breast cancer cells proliferation and inflammatory cytokines secretion. J Exp Clin Cancer Res. 29:922010. View Article : Google Scholar : PubMed/NCBI

18 

He W, Liu Q, Wang L, Chen W, Li N and Cao X: TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 44:2850–2859. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Hiratsuka S, Watanabe A, Sakurai Y, et al: The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol. 10:1349–1355. 2008. View Article : Google Scholar : PubMed/NCBI

20 

Zhang YB, He FL, Fang M, et al: Increased expression of Toll-like receptors 4 and 9 in human lung cancer. Mol Biol Rep. 36:1475–1481. 2009. View Article : Google Scholar : PubMed/NCBI

21 

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.

22 

Campo E, Merino MJ, Liotta L, Neumann R and Stetler-Stevenson W: Distribution of 72KD type IV collagenase in nonneoplastic and neoplastic thyroid tissue. Hum Pathol. 23:1395–1401. 1992. View Article : Google Scholar : PubMed/NCBI

23 

Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI

24 

Zhang D, Chen ZG, Liu SH, et al: Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating beta-catenin. Acta Pharmacol Sin. 34:176–184. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Mendez M, Custodio A and Provencio M: New molecular targeted therapies for advanced non-small-cell lung cancer. J Thorac Dis. 3:30–56. 2011.PubMed/NCBI

26 

Yao H and Rahman I: Current concepts on the role of inflammation in COPD and lung cancer. Curr Opin Pharmacol. 9:375–383. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Bauer AK, Dixon D, DeGraff LM, et al: Toll-like receptor 4 in butylated hydroxytoluene-induced mouse pulmonary inflammation and tumorigenesis. J Natl Cancer Inst. 97:1778–1781. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Bauer AK, Fostel J, Degraff LM, et al: Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis. Mol Cancer. 8:1072009. View Article : Google Scholar : PubMed/NCBI

29 

Szczepanski MJ, Czystowska M, Szajnik M, et al: Triggering of Toll-like receptor 4 expressed on human head and neck squamous cell carcinoma promotes tumor development and protects the tumor from immune attack. Cancer Res. 69:3105–3113. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Huang B, Zhao J, Li H, et al: Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 65:5009–5014. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Hua D, Liu MY, Cheng ZD, et al: Small interfering RNA-directed targeting of Toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity. Mol Immunol. 46:2876–2884. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Ahmed A, Wang JH and Redmond HP: Silencing of TLR4 increases tumor progression and lung metastasis in a murine model of breast cancer. Ann Surg Oncol. 20(Suppl 3): S389–S396. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Kusmartsev S and Gabrilovich DI: Immature myeloid cells and cancer-associated immune suppression. Cancer Immunol Immunother. 51:293–298. 2002. View Article : Google Scholar : PubMed/NCBI

35 

Gatti G, Quintar AA, Andreani V, et al: Expression of Toll-like receptor 4 in the prostate gland and its association with the severity of prostate cancer. Prostate. 69:1387–1397. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Starska K, Forma E, Brys M, et al: The expression of TLR pathway molecules in peripheral blood mononuclear cells and their relationship with tumor invasion and cytokine secretion in laryngeal carcinoma. Adv Med Sci. 57:124–135. 2012. View Article : Google Scholar : PubMed/NCBI

37 

Hartmann E, Wollenberg B, Rothenfusser S, et al: Identification and functional analysis of tumor-infiltrating plasmacytoid dendritic cells in head and neck cancer. Cancer Res. 63:6478–6487. 2003.PubMed/NCBI

38 

Oka N, Tanimoto S, Taue R, et al: Role of phosphatidylinositol-3 kinase/Akt pathway in bladder cancer cell apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand. Cancer Sci. 97:1093–1098. 2006. View Article : Google Scholar : PubMed/NCBI

39 

Kai K, D’Costa S, Sills RC and Kim Y: Inhibition of the insulin-like growth factor 1 receptor pathway enhances the antitumor effect of cisplatin in human malignant mesothelioma cell lines. Cancer Lett. 278:49–55. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Li D, Jin Y, Sun Y, Lei J and Liu C: Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo. Int J Oncol 45: 813-821, 2014.
APA
Li, D., Jin, Y., Sun, Y., Lei, J., & Liu, C. (2014). Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo. International Journal of Oncology, 45, 813-821. https://doi.org/10.3892/ijo.2014.2479
MLA
Li, D., Jin, Y., Sun, Y., Lei, J., Liu, C."Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo". International Journal of Oncology 45.2 (2014): 813-821.
Chicago
Li, D., Jin, Y., Sun, Y., Lei, J., Liu, C."Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo". International Journal of Oncology 45, no. 2 (2014): 813-821. https://doi.org/10.3892/ijo.2014.2479
Copy and paste a formatted citation
x
Spandidos Publications style
Li D, Jin Y, Sun Y, Lei J and Liu C: Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo. Int J Oncol 45: 813-821, 2014.
APA
Li, D., Jin, Y., Sun, Y., Lei, J., & Liu, C. (2014). Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo. International Journal of Oncology, 45, 813-821. https://doi.org/10.3892/ijo.2014.2479
MLA
Li, D., Jin, Y., Sun, Y., Lei, J., Liu, C."Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo". International Journal of Oncology 45.2 (2014): 813-821.
Chicago
Li, D., Jin, Y., Sun, Y., Lei, J., Liu, C."Knockdown of toll-like receptor 4 inhibits human NSCLC cancer cell growth and inflammatory cytokine secretion in vitro and in vivo". International Journal of Oncology 45, no. 2 (2014): 813-821. https://doi.org/10.3892/ijo.2014.2479
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