Skip to main content

Advertisement

SpringerLink
Log in

COX-2 Gene increases tongue cancer cell proliferation and invasion through VEGF-C pathway

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

COX-2 induces the proliferation and invasion of oral squamous cell carcinoma. In the present study, the role of the COX-2 gene in the tongue cancer cell proliferation and invasion was investigated. A short hairpin RNA (shRNA)method was used to knock down COX-2 gene expression and investigate the relationship between COX-2 and VEGF-C, and the role of the COX-2 gene for proliferation and invasion was also investigated in the tongue cancer cell Tca8113. COX-2 gene overexpressed in tongue cancer cell line. Suppressing the expression of COX-2 by shRNA could decrease cell proliferation comparing with control shRNA. Nevertheless, depressing COX-2 gene expression by shRNA reduced VEGF-C expression on both mRNA and protein levels. VEGF-C gene expression could be regulated by COX-2 gene. Our results suggested that COX-2 played essential roles in the proliferation and metastasis of tongue cancer, and COX-2 could serve as a potential chemotherapy target for tongue cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Kruaysawat W, Aekplakorn W, Chapman RS. Survival time and prognostic factors of oral cancer in Ubon Ratchathani cancer center. J Med Assoc Thai. 2010;93(3):278–84.

    PubMed  Google Scholar 

  2. Sun CZ, Chen FJ, Zeng ZY, Deng LF, Yang AK, Chen YF. Treatment and prognostic analysis of 92 cases with advanced mobile tongue squamous cell carcinoma. Zhonghua Kou Qiang Yi Xue Za Zhi. 2006;41(11):650–3.

    PubMed  Google Scholar 

  3. Estilo CL, O-charoenrat P, Talbot S, Socci ND, Carlson DL, Ghossein R, Williams T, Yonekawa Y, Ramanathan Y, Boyle JO, Kraus DH, patel S, Shaha AR, Wong RJ, Huryn JM, Shah JP, Singh B. Oral tongue cancer gene expression profiling: identification of novel potential prognosticators by oligonucleotide microarray analysis. BMC Cancer. 2009;12(9):11.

    Article  Google Scholar 

  4. Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002;94(4):252–66.

    PubMed  CAS  Google Scholar 

  5. Wang R, Wang X, Lin F, Gao P, Dong K, Zhang HZ. shRNA-targeted cyclooxygenase (COX)-2 inhibits proliferation, reduces invasion and enhances chemosensitivity in laryngeal carcinoma cells. Mol Cell Biochem. 2008;317(1–2):179–88.

    Article  PubMed  CAS  Google Scholar 

  6. Zhao X, Goswami M, Pokhriyal N, Ma H, Du H, Yao J, Victor TA, Polyak K, Sturgis CD, Band H, Band V. Cyclooxygenase-2 expression during immortalization and breast cancer progression. Cancer Res. 2008;68(2):467–75.

    Article  PubMed  CAS  Google Scholar 

  7. Patel S, Chiplunkar S. Role of cyclooxygenase-2 in tumor progression and immune regulation in lung cancer. Indian J Biochem Biophys. 2007;44(6):419–28.

    PubMed  CAS  Google Scholar 

  8. Forones NM, Kawamura KY, Segreto HR, Artigiani Neto R, Focchi GR, Oshima CT. Expression of COX-2 in stomach carcinogenesis. J Gastrointest Cancer. 2008;39(1–4):4–10.

    Article  PubMed  CAS  Google Scholar 

  9. Miyashita M, Makino H, Katsuta M, Nomura T, Shinji S, Kashiwabara M, Takahashi K, Kudo M, Ishiwata T, Naito Z, Tajiri T. Cyclo-oxygenase-2 over-expression is associated with human esophageal squamous cell carcinoma. J Nippon Med Sch. 2006;73(6):308–13.

    Article  CAS  Google Scholar 

  10. Yamac D, Celenkoglu G, Coskun U, Akyurek N, Akcali Z, Dursun A, Koybasioglu F. Prognostic importance of COX-2 expression in patients with colorectal cancer. Pathol Res Pract. 2005;201(7):497–502.

    Article  PubMed  CAS  Google Scholar 

  11. Menczer J. Cox-2 expression in ovarian malignancies: a review of the clinical aspects. Eur J Obstet Gynecol Reprod Biol. 2009;146(2):129–312.

    Article  PubMed  CAS  Google Scholar 

  12. Kern MA, Schirmacher P, Breinig M. Significance of cyclooxygenase-2 as a chemotherapeutic target in hepatocellular carcinoma. Verh Dtsch Ges Pathol. 2007;91:257–68.

    PubMed  CAS  Google Scholar 

  13. Cao.Y, Prescott SM. Many action of cyclooxygenase-2 in cellular dynamics and cancer. J Cell Physiol. 2002;190(3):279–86.

    Article  PubMed  Google Scholar 

  14. Eberhart CE, Coffey RJ, Radhika A, Giardiello FM, Ferrenbach S, DuBois RN. Up-regulation of cyclooxygenase 2 gene expression in human colorectal adenomas and adenocarcinomas. Gastroenterology. 1994;107(4):1183–888.

    PubMed  CAS  Google Scholar 

  15. Evans JF, Kargman SL. Cancer and cyclooxygenase-2 (COX-2) inhibition. Curr Pharm Des. 2004;10(6):627–34.

    Article  PubMed  CAS  Google Scholar 

  16. Prescott SM. Is cyclooxygenase-2 the alpha and the omega in cancer? J Clin Invest. 2000;105(11):1511–3.

    Article  PubMed  CAS  Google Scholar 

  17. Li WZ, Huo QJ, Wang XY, Xu F. (2010).Inhibitive effect of celecoxib on the adhesion and invasion of human tongue squamous carcinoma cells to extracellular matrix via down regulation of MMP-2 expression. Prostaglandins Other Lipid Mediat (Epub ahead of print).

  18. Kwak YE, Jeon NK, Kim J, Lee EJ. The cyclooxygenase-2 selective inhibitor celecoxib suppresses proliferation and invasiveness in the human oral squamous carcinoma. Ann N Y Acad Sci. 2007;1095:99–112.

    Article  PubMed  CAS  Google Scholar 

  19. Stöllberger C, Finsterer J. Side effects of conventional nonsteroidal anti-inflammatory drugs and celecoxib: more similarities than differences. South Med J. 2004;97(2):209.

    Article  PubMed  Google Scholar 

  20. Chang CH, Shau WY, Kuo CW, Chen ST, Lai. Increased risk of stroke associated with nonsteroidal anti-inflammatory drugs: a nationwide case-crossover study. Stroke. 2010;41(9):1884–90.

    Article  PubMed  CAS  Google Scholar 

  21. Bhattacharjee RN, Timoshenko AV, Cai J, Lala PK. (2010) Relationship between cyclooxygenase-2 and human epidermal growth factor receptor 2 in vascular endothelial growth factor C up-regulation and lymphangiogenesis in human breast cancer. Cancer Sci (Epub ahead of print).

  22. Di JM, Zhou J, Zhou XL, Gao X, Shao CQ, Pang J, Sun QP, Zhang Y, Ruan XX. Cyclooxygenase-2 expression is associated with vascular endothelial growth factor-C and lymph node metastases in human prostate cancer. Arch Med Res. 2009;40(4):268–75.

    Article  PubMed  CAS  Google Scholar 

  23. Bruno T, Desantis A, Bossi G, Di Agostino S, Sorino C, De Nicola F, Iezzi S, Franchitto A, Benassi B, Galanti S, La Rosa F, Floridi A, Bellacosa A, Passananti C, Blandino G, Fanciulli M. Che-1 promotes tumor cell survival by sustaining mutant p53 transcription and inhibiting DNA damage response activation. Cancer Cell. 2010;18(2):122–34.

    Article  PubMed  CAS  Google Scholar 

  24. Abbasi M, Lavasanifar A, Berthiaume LG, Weinfeld M, Uludağ H. (2010) Cationic polymer-mediated small interfering RNA delivery for P-glycoprotein down-regulation in tumor cells. Cancer (Epub ahead of print).

  25. Wang YH, Chen YF, Guo ZM, Zhang Q, Liu TR, Chen FJ. Reasons for recurrence and prognostic analysis of early stage squamous cell carcinoma of the oral tongue. Ai Zheng. 2009;28(5):524–7.

    PubMed  Google Scholar 

  26. Alitalo K, Tammela T, Petrova TV. Lymphangiogenesis in development and human disease. Nature. 2005;438(7070):946–53.

    Article  PubMed  CAS  Google Scholar 

  27. Achen MG, Stacker SA. Tumor lymphangiogenesis and metastatic spread-new players begin to emerge. Int J Cancer. 2006;119(8):1755–60.

    Article  PubMed  CAS  Google Scholar 

  28. Pepper MS, Tille JC, Nisato R, Skobe M. Lymphangiogenesis and tumor metastasis. Cell Tissue Res. 2003;314(1):167–77.

    Article  PubMed  CAS  Google Scholar 

  29. Yonemura Y, Endo Y, Fujita H, Fushida S, Ninomiya I, Bandou E, Taniguchi K, Miwa K, Ohoyama S, Sugiyama K, Sasaki T. Role of vascular endothelial growth factor C expression in the development of lymph node metastasis in gastric cancer. Clin Cancer Res. 1999;5(7):1823–9.

    PubMed  CAS  Google Scholar 

  30. Su JL, Shih JY, Yen ML, Jeng YM, Chang CC, Hsieh CY, Wei LH, Yang PC, Kuo ML. Cyclooxygenase-2 induces EP-1 and HER-2/Neu-dependent vascular endothelial growth factor-c up-regu-latin: a novel mechanism of lymphangiogensis in lung adenocarcinomn. Cancer Res. 2004;64(2):554–64.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study has been supported by the Guangdong for Natural Scientific Fund (7301082) of China.

Conflict of interest

All authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Head and Neck Surgery, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, Guangdong, People’s Republic of China

    Yan-Hong Wang, An-Kui Yang & Yan-Feng Chen

  2. Department of Experimental Research, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, Guangdong, People’s Republic of China

    Ming-Wei Wu & Jian Sun

  3. Department of Imaging and Interventional Center, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, Guangdong, People’s Republic of China

    Wei-Dong Zhang

  4. Department of Infectious disease ICU, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China

    Yan-Hong Wang

  5. Department of Otolaryngology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China

    Tian-Run Liu

Authors
  1. Yan-Hong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming-Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. An-Kui Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wei-Dong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tian-Run Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yan-Feng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yan-Feng Chen.

Additional information

Yan-Hong Wang and Ming-Wei Wu contributed equally to the article as first author.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, YH., Wu, MW., Yang, AK. et al. COX-2 Gene increases tongue cancer cell proliferation and invasion through VEGF-C pathway. Med Oncol 28 (Suppl 1), 360–366 (2011). https://doi.org/10.1007/s12032-010-9737-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-010-9737-3

Keywords

Search

Navigation