[Mechanisms of inhibiting proliferation and inducing apoptosis of human gastric cancer cell line SGC7901 by ursolic acid]

Ai Zheng. 2006 Apr;25(4):432-7.
[Article in Chinese]

Abstract

Background & objective: Some studies have showed that ursolic acid (UA) can inhibit proliferation and induce apoptosis of many tumor cell lines, however its effect on gastric cancer cells has rarely been reported. Cyclooxygenase-2 (COX-2) is highly expressed in various precursor lesions and cancerous tissues. This study was to investigate the effect of UA on COX-2, Bcl-2 and Bax expression in human gastric cancer cell line SGC7901, and explore its potential mechanisms of inhibiting proliferation and inducing apoptosis.

Methods: MTT assay was used to observe the effect of UA (0, 10, 20, 30, 40 micromol/L) on proliferation of SGC7901 cells. Cell apoptosis was observed by fluorescence microscopy when treated with UA for 24 h. Cell cycle and apoptosis were analyzed by flow cytometry (FCM). The expression of COX-2, Bcl-2 and Bax was detected by Western blot. The level of prostaglandin E2 (PGE2) was measured by radioimmunoassay (RIA).

Results: UA (20-40 micromol/L) significantly inhibited the proliferation of SGC7901 cells in dose-and time-dependent manners, the IC50 value of UA at 12 h, 24 h, 36 h, 48 h were (57.50+/-1.18) micromol/L, (34.28+/-2.05) micromol/L, (27.54+/-1.11) micromol/L, and (24.83+/-1.02) micromol/L, respectively. When treated with 20-40 micromol/L UA for 24 h, SGC7901 cells were arrested at G0/G1 phase, and the apoptosis rates were (9.10+/-2.39)%, (26.30+/-1.25)%, and (35.20+/-2.26)%, respectively; meanwhile, COX-2 expression and its catalysate PGE2 were decreased, Bcl-2 expression was also decreased, whereas Bax expression was unchanged.

Conclusion: UA could inhibit proliferation and induce apoptosis of SGC7901 cells through arresting cell cycle, inhibiting COX-2 expression to reduce PGE2 production and down-regulate Bcl-2 expression.

Publication types

  • English Abstract
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Triterpenes / administration & dosage
  • Triterpenes / pharmacology*
  • Ursolic Acid
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Proto-Oncogene Proteins c-bcl-2
  • Triterpenes
  • bcl-2-Associated X Protein
  • Cyclooxygenase 2
  • Dinoprostone