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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
October-2015 Volume 34 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 34 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

Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell

  • Authors:
    • Wenwu Wang
    • Xiaoyan Qi
    • Minghua Wu
  • View Affiliations / Copyright

    Affiliations: Hunan Provincial Tumor Hospital and Τhe Affiliated Tumor, Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410078, P.R. China, Department of Medicine Oncology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian 350025, P.R. China
  • Pages: 2115-2125
    |
    Published online on: August 4, 2015
       https://doi.org/10.3892/or.2015.4170
  • 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

The aim of the present study was to examine the relationship between DR4 methylation status and gene expression and to determine whether DR4 methylation status affects TRAIL-induced apoptosis in lung squamous carcinoma cells. MSP, RT-PCR and western blot analysis were applied to detect the methylation status and gene expression. An MTT assay was used to detect the cell proliferation inhibition rate and flow cytometry was utilized to detect the apoptotic rate. The results showed that there was no association of the apoptotic rate with the clinicopathological characteristics for 80.6% of 36 lung squamous carcinoma patients in the methylation status (P>0.05). In the lung squamous carcinoma patients, the probability of DR4 low expression was approximately 58.3%, which may be associated with DR4 promoter methylation. The results also showed that a low expression of DR4 was correlated with the prognosis of patients. The in vitro experiments suggested DR4 genes of H226 and SK-MES-1 cells were in the methylation status and their mRNA and proteins had a low expression. Following intervention with 5-Aza-CdR, the DR4 genes of H226 and SK-MES-1 cells were in the unmethylation status and their mRNA and protein expression was significantly upregulated compared with the pre-interference ones, with differences being statistically significant (P<0.05). In addition, following interference with 5-Aza-CdR, H226 and SK-MES-1 cells became significantly sensitive to TRAIL (P<0.05). The results revealed 5-Aza‑CdR was able to reverse DR4 methy­lation status to upregulate its expression, thereby increasing the TRAIL-induced apoptosis in lung squamous carcinoma cells. Therefore, combining 5-Aza-CdR and TRAIL is a new strategy for treating lung squamous carcinoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

Figure 11

Figure 12

View References

1 

Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA: Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 83:584–594. 2008. View Article : Google Scholar : PubMed/NCBI

2 

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 : PubMed/NCBI

3 

Azzoli CG, Baker S Jr, Temin S, Pao W, Aliff T, Brahmer J, Johnson DH, Laskin JL, Masters G, Milton D, et al American Society of Clinical Oncology: American Society of Clinical Oncology Clinical Practice Guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol. 27:6251–6266. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Zhang X, Zhao J, Zhu W, Gou H, Cao D, Yang Y, Huang Y and Yi C: Synergistic effect of subtoxic-dose cisplatin and TRAIL to mediate apoptosis by down-regulating decoy receptor 2 and up-regulating caspase-8, caspase-9 and Bax expression on NCI-H460 and A549 Cells. Iran J Basic Med Sci. 16:710–718. 2013.PubMed/NCBI

5 

Stegehuis JH, de Wilt LH, de Vries EG, Groen HJ, de Jong S and Kruyt FA: TRAIL receptor targeting therapies for non-small cell lung cancer: Current status and perspectives. Drug Resist Updat. 13:2–15. 2010. View Article : Google Scholar

6 

Luster TA, Carrell JA, McCormick K, Sun D and Humphreys R: Mapatumumab and lexatumumab induce apoptosis in TRAIL-R1 and TRAIL-R2 antibody-resistant NSCLC cell lines when treated in combination with bortezomib. Mol Cancer Ther. 8:292–302. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Jung Y-H, Heo J, Lee YJ, Kwon TK and Kim Y-H: Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5. Life Sci. 86:351–357. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Schaefer U, Voloshanenko O, Willen D and Walczak H: TRAIL: A multifunctional cytokine. Front Biosci. 12:3813–3824. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Dillon CP, Oberst A, Weinlich R, Janke LJ, Kang TB, Ben-Moshe T, Mak TW, Wallach D and Green DR: Survival function of the FADD-CASPASE-8-cFLIP(L) complex. Cell Reports. 1:401–407. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Maldonado ME, Bousserouel S, Gossé F, Lobstein A and Raul F: Implication of NF-κB and p53 in the expression of TRAIL-death receptors and apoptosis by apple procyanidins in human metastatic SW620 cells. Biomedica. 30:577–586. 2010. View Article : Google Scholar

11 

Haag C, Stadel D, Zhou S, Bachem MG, Möller P, Debatin KM and Fulda S: Identification of c-FLIPL and c-FLIPS as critical regulators of death receptor-induced apoptosis in pancreatic cancer cells. Gut. 60:225–237. 2010. View Article : Google Scholar

12 

Falschlehner C, Emmerich CH, Gerlach B and Walczak H: TRAIL signalling: Decisions between life and death. Int J Biochem Cell Biol. 39:1462–1475. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Earel JK Jr, VanOosten RL and Griffith TS: Histone deacetylase inhibitors modulate the sensitivity of tumor necrosis factor-related apoptosis-inducing ligand-resistant bladder tumor cells. Cancer Res. 66:499–507. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Papageorgiou A, Lashinger L, Millikan R, Grossman HB, Benedict W, Dinney CP and McConkey DJ: Role of tumor necrosis factor-related apoptosis-inducing ligand in interferon-induced apoptosis in human bladder cancer cells. Cancer Res. 64:8973–8979. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Lee KH, Lim SW, Kim HG, Kim DY, Ryu SY, Joo JK, Kim JC and Lee JH: Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma. Langenbecks Arch Surg. 394:661–670. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Bae SI, Cheriyath V, Jacobs BS, Reu FJ and Borden EC: Reversal of methylation silencing of Apo2L/TRAIL receptor 1 (DR4) expression overcomes resistance of SK-MEL-3 and SK-MEL-28 melanoma cells to interferons (IFNs) or Apo2L/TRAIL. Oncogene. 27:490–498. 2008. View Article : Google Scholar

17 

Suzuki M, Shigematsu H, Shivapurkar N, Reddy J, Miyajima K, Takahashi T, Gazdar AF and Frenkel EP: Methylation of apoptosis related genes in the pathogenesis and prognosis of prostate cancer. Cancer Lett. 242:222–230. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Horak P, Pils D, Haller G, Pribill I, Roessler M, Tomek S, Horvat R, Zeillinger R, Zielinski C and Krainer M: Contribution of epigenetic silencing of tumor necrosis factor-related apoptosis inducing ligand receptor 1 (DR4) to TRAIL resistance and ovarian cancer. Mol Cancer Res. 3:335–343. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Eramo A, Pallini R, Lotti F, Sette G, Patti M, Bartucci M, Ricci-Vitiani L, Signore M, Stassi G, Larocca LM, et al: Inhibition of DNA methylation sensitizes glioblastoma for tumor necrosis factor-related apoptosis-inducing ligand-mediated destruction. Cancer Res. 65:11469–11477. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Keating GM: Azacitidine: A review of its use in higher-risk myelodysplastic syndromes/acute myeloid leukaemia. Drugs. 69:2501–2518. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Cataldo VD, Cortes J and Quintás-Cardama A: Azacitidine for the treatment of myelodysplastic syndrome. Expert Rev Anticancer Ther. 9:875–884. 2009. View Article : Google Scholar : PubMed/NCBI

22 

Kaminskas E, Farrell A, Abraham S, Baird A, Hsieh LS, Lee SL, Leighton JK, Patel H, Rahman A, Sridhara R, et al FDA: Approval summary: Azacitidine for treatment of myelodysplastic syndrome subtypes. Clin Cancer Res. 11:3604–3608. 2005. View Article : Google Scholar : PubMed/NCBI

23 

Vaitkienė P, Skiriutė D, Skauminas K and Tamašauskas A: Associations between TFPI-2 methylation and poor prognosis in glioblastomas. Medicina (Kaunas). 48:345–349. 2012.

24 

Dong SW, Ma L, Xu N, Yan HQ, Liu HY, Li YW and Zhang P: Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer. Neoplasma. 58:89–95. 2011. View Article : Google Scholar

25 

Lin CT, Lai HC, Lee HY, Lin WH, Chang CC, Chu TY, Lin YW, Lee KD and Yu MH: Valproic acid resensitizes cisplatin-resistant ovarian cancer cells. Cancer Sci. 99:1218–1226. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Avraham A, Cho SS, Uhlmann R, Polak ML, Sandbank J, Karni T, Pappo I, Halperin R, Vaknin Z, Sella A, et al: Tissue specific DNA methylation in normal human breast epithelium and in breast cancer. PLoS One. 9:e918052014. View Article : Google Scholar : PubMed/NCBI

27 

Yan H and Sun J: Methylation status of WWOX gene promoter CpG islands in epithelial ovarian cancer and its clinical significance. Biomed Rep. 1:375–378. 2013.

28 

Baylin SB and Jones PA: A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 11:726–734. 2011. View Article : Google Scholar : PubMed/NCBI

29 

Tan S, Sun C, Wei X, Li Y and Wu Y, Yan Z, Feng F, Wang J and Wu Y: Quantitative assessment of lung cancer associated with genes methylation in the peripheral blood. Exp Lung Res. 39:182–190. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Kupčinskaitė-Noreikienė R, Skiecevičienė J, Jonaitis L, Ugenskienė R, Kupčinskas J, Markelis R, Baltrėnas V, Sakavičius L, Semakina I, Grižas S, et al: CpG island methylation of the MLH1, MGMT, DAPK, and CASP8 genes in cancerous and adjacent noncancerous stomach tissues. Medicina (Kaunas). 49:361–366. 2013.

31 

Balgkouranidou I, Liloglou T and Lianidou ES: Lung cancer epigenetics: Emerging biomarkers. Biomarkers Med. 7:49–58. 2013. View Article : Google Scholar

32 

Xie F-W, Peng Y-H, Wang W-W, Chen X, Chen X, Li J, Yu ZY and Ouyang XN: Influence of UGT1A1 gene methylation level in colorectal cancer cells on the sensitivity of the chemotherapy drug CPT-11. Biomed Pharmacother. 68:825–831. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Xie F-W, Peng Y-H, Chen X, Chen X, Li J, Yu ZY, Wang WW and Ouyang XN: Regulation and expression of aberrant methylation on irinotecan metabolic genes CES2, UGT1A1 and GUSB in the in-vitro cultured colorectal cancer cells. Biomed Pharmacother. 68:31–37. 2014. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang W, Qi X and Wu M: Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell. Oncol Rep 34: 2115-2125, 2015.
APA
Wang, W., Qi, X., & Wu, M. (2015). Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell. Oncology Reports, 34, 2115-2125. https://doi.org/10.3892/or.2015.4170
MLA
Wang, W., Qi, X., Wu, M."Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell". Oncology Reports 34.4 (2015): 2115-2125.
Chicago
Wang, W., Qi, X., Wu, M."Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell". Oncology Reports 34, no. 4 (2015): 2115-2125. https://doi.org/10.3892/or.2015.4170
Copy and paste a formatted citation
x
Spandidos Publications style
Wang W, Qi X and Wu M: Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell. Oncol Rep 34: 2115-2125, 2015.
APA
Wang, W., Qi, X., & Wu, M. (2015). Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell. Oncology Reports, 34, 2115-2125. https://doi.org/10.3892/or.2015.4170
MLA
Wang, W., Qi, X., Wu, M."Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell". Oncology Reports 34.4 (2015): 2115-2125.
Chicago
Wang, W., Qi, X., Wu, M."Effect of DR4 promoter methylation on the TRAIL‑induced apoptosis in lung squamous carcinoma cell". Oncology Reports 34, no. 4 (2015): 2115-2125. https://doi.org/10.3892/or.2015.4170
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