Antiproliferative effects of celecoxib in Hep-2 cells through telomerase inhibition and induction of apoptosis

Asian Pac J Cancer Prev. 2014;15(12):4919-23. doi: 10.7314/apjcp.2014.15.12.4919.

Abstract

Background: To investigate the effect of celecoxib on telomerase activity and apoptosis in a human laryngeal squamous carcinoma cell line (Hep-2 cells).

Materials and methods: 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.

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.

Conclusions: 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.

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Celecoxib
  • Cell Proliferation / drug effects*
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Flow Cytometry
  • Humans
  • Immunoenzyme Techniques
  • Laryngeal Neoplasms / drug therapy
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology*
  • Pyrazoles / pharmacology*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sulfonamides / pharmacology*
  • Telomerase / antagonists & inhibitors*
  • Telomerase / genetics
  • Telomerase / metabolism
  • Tumor Cells, Cultured

Substances

  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • TERT protein, human
  • Telomerase
  • Celecoxib