Abstract

To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). The growth inhibition rate of Hep-2 cells in vitro was measured by MTT assay, and apoptosis by TUNEL assay and flow cytometry (FCM). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. The mRNA expression of human telomerase RNA component(hTR), human telomerase reverse transcriptase (hTERT) and human telomerase-associated protein(hTEP1) was determined by RT-PCR assay. Expression of Bax and Bcl-2 proteins was assessed by Western blotting. Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. Celecoxib had the antiproliferative and pro-apoptotic effect in Hep-2 cells. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may thus play an important role in telomerase activity as well as apoptosis.

Highlights

  • Larynx cancer is 3rd common familiar carcinomas of the head neck cancers and nearly 4, 000 larynx cancer patients die each year in America (Jemal et al, 2010)

  • Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease human telomerase reverse transcriptase (hTERT) mRNA and Bcl-2 protein expression and increase Bax protein expression, Prostaglandin E2 (PGE2) had no effect on telomerase

  • Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2

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Summary

Introduction

Larynx cancer is 3rd common familiar carcinomas of the head neck cancers and nearly 4, 000 larynx cancer patients die each year in America (Jemal et al, 2010). Squamous cell carcinoma accounts for 90% of all malignancies of the larynx and chromosomal aberrations accumulate can result in a more aggressive cancer phenotype as disease stage advance (Guo et al, 2012). Upregulated expression of COX-2 is an early event during carcinogenesis, and is mostly associated with poor prognosis as it promotes tumor cell proliferation, angiogenesis, invasion (Harizi et al, 2002). To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells). The TRAP-ELISA method was used to determine telomerase activity in Hep-2 cells. Results: Celecoxib can inhibit proliferation and induce apoptosis in a dose- and time-dependent manner, repress telomerase activity, decrease hTERT mRNA and Bcl-2 protein expression and increase Bax protein expression, PGE2 had no effect on telomerase. Apoptosis was accompanied by a decrease in telomerase activity which was directly correlated with hTERT mRNA and up-regulation of Bax/Bcl-2. Bcl-2 may play an important role in telomerase activity as well as apoptosis

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Conclusion

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