Effect of celecoxib on proliferation, apoptosis, and survivin expression in human glioma cell line U251

Chin J Cancer. 2010 Mar;29(3):294-9. doi: 10.5732/cjc.009.10290.

Abstract

Background and objective: Celecoxib, one of the new generation of non-steroidal anti-inflammatory drugs (NSAIDs), has a specific inhibitory effect on COX-2. Studies have shown that celecoxib can inhibit the proliferation of tumor cells and induce cell apoptosis, which has been confirmed in colorectal tumors and familial adenomatous polyposis. This study explored the effect of celecoxib on the proliferation and apoptosis of human glioma cell line U251 and elucidated the correlation between the effect of celecoxib and the expression of survivin.

Methods: U251 cells were treated with different concentrations of celecoxib. Cell morphologic changes were observed by optical microscopy. MTT assay was used to detect the absorbance value and to calculate inhibition and survival rates. The rates of apoptosis of U251 cells after 48 h of treatment with celecoxib were assessed by flow cytometry. The expression of survivin was analyzed by immunocytochemistry (ICC) and Western blot analysis. The expression of survivin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR).

Results: Significant morphologic changes were shown in U251 cells after treatment with celecoxib. The MTT assay results revealed that celecoxib inhibited the proliferation of U251 cells and the inhibitory rates significantly increased in a dose-and time-dependent manner. After 48 h of treatment with celecoxib, the apoptotic cells could be obviously observed, and the apoptosis rate significantly increased with increases in concentrations of celecoxib. The expression of survivin was observed in the control group, however, the expression of survivin was significantly down-regulated as the concentration of celecoxib increased. The level of survivin mRNA expression in U251 cells was significantly down-regulated after treatment with different concentrations of celecoxib (P < 0.05).

Conclusions: The inhibition of proliferation and apoptosis in U251 cells could be induced by celecoxib in a dose-and time-dependent manner, and its mechanism might be the downregulation of the expression of survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Celecoxib
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Glioma / metabolism
  • Glioma / pathology*
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism*
  • Pyrazoles / administration & dosage
  • Pyrazoles / pharmacology*
  • RNA, Messenger / metabolism
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Survivin

Substances

  • BIRC5 protein, human
  • Cyclooxygenase Inhibitors
  • Inhibitor of Apoptosis Proteins
  • Pyrazoles
  • RNA, Messenger
  • Sulfonamides
  • Survivin
  • Celecoxib