[Therapeutic effect of in vitro 5-aza-2'-deoxycytidine combined with imatinib on gastrointestinal stromal tumor]

Zhonghua Wei Chang Wai Ke Za Zhi. 2012 Mar;15(3):266-70.
[Article in Chinese]

Abstract

Objective: To investigate the impact of 5-aza-2'-deoxycytidine(5-aza-CdR) combined with imatinib on the proliferation, motility, invasion, and apoptosis of gastrointestinal stromal tumors(GIST) cells in vitro.

Methods: MTT assay was used to investigate the effect of the two agents on proliferation of GIST882. Plate colony forming assay was used to determine the number of colony-forming. Motility and invasion abilities were tested to evaluate the inhibitory effect of each agent. Flow cytometry was used to observe apoptosis and cell cycle.

Results: 5-aza-CdR or imatinib effectively inhibited the growth of GIST882 cells in concentration- and time-dependent manner. The inhibitory rate of combined treatment using 5-aza-CdR and imatinib was significantly higher than that of 5-aza-CdR or imatinib alone(P<0.05). After treatment for 48 h, the apoptosis rates of 5-aza-CdR group (1000 μg/L) and imatinib group (100 μmol/L) were (11.7±1.2)% and (14.6±0.8)%, respectively. Compared with the control group (2.8±0.3)%, the difference was statistically significant(P=0.000). Furthermore, the difference in apoptosis rate was significant between combined treatment group (19.4±1.1)% and single drug treatment group(vs. 5-aza-CdR group, P=0.000, vs. imatinib group, P=0.013). 5-aza-CdR raised G0/G1 ratio and reduced S ratio of GIST882. Imatinib and combined group had no apparent influence on the cell cycle of GIST882 cells.

Conclusion: 5-aza-CdR may be a potential agent of GIST treatment in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology*
  • Apoptosis / drug effects
  • Azacitidine / analogs & derivatives*
  • Azacitidine / pharmacology
  • Benzamides / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Decitabine
  • Gastrointestinal Stromal Tumors / etiology
  • Gastrointestinal Stromal Tumors / pathology*
  • Humans
  • Imatinib Mesylate
  • Piperazines / pharmacology*
  • Pyrimidines / pharmacology*

Substances

  • Antimetabolites, Antineoplastic
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Decitabine
  • Imatinib Mesylate
  • Azacitidine