[Study on the relationship between the inhibitors of apoptosis proteins and the apoptosis of myelodysplastic syndrome cell line cells induced by aclacinomycin in vitro]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2004 Oct;12(5):606-9.
[Article in Chinese]

Abstract

To explore the correlation between the cellular inhibitors of apoptosis proteins (cIAPs) and the apoptosis of myelodysplastic syndrome (MDS) cell line (RAEB type) cells induced by aclacinomycin (ACM), the apoptosis of MDS cell line MUTZ-1 cells induced by ACM was analyzed with terminal deoxyribonucleotidy transferase mediated dUTP-biotin nick end labeling (TUNEL) technique. By using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), the expression levels of cIAP-1 and cIAP-2 mRNA in MUTZ-1 cells were assayed. The results showed as follow: (1) Using 0.5 micromol/L, 1.0 micromol/L ACM treated cells for 24 hours, the relative expression level of cIAP-1 mRNA (cIAP-1/GAPDH) was lower than those in the untreated cell group (P=0.002, 0.0002, respectively). (2) Using 0.5 micromol/L ACM treated for 6, 12, 24 hours, the relative expression level of cIAP-1 mRNA was 0.95 +/- 0.04, 0.73 +/- 0.05, 0.38 +/- 0.07, respectively and the relative expression level of cIAP-1 mRNA was correlated negatively with the time treated by ACM (r=-0.996, P <0.01). (3) Using 0.5 micromol/L ACM treated for 3, 6, 12, 24 hours, the relative expression level of cIAP-2 mRNA was 1.17 +/- 0.06, 0.91 +/- 0.03, 0.69 +/- 0.07 and 0.00 +/- 0.00, respectively and relative expression level of CIAP-2 mRNA was correlated negatively with the time treated by ACM (r=-0.091, P <0.01). (4) The percentages of TUNEL positive cells were correlated negatively with the relative expression level of CIAP1 and CIAP2 mRNA (r=-0.984, -0.959 and P=0.002, 0.013 respectively) when treated with increasing concentration of ACM. In conclusion, ACM can induce significantly MUTZ-1 cell apoptosis via suppressing expression of anti-apoptotic gene cIAP-1 and cIAP-2 mRNA.

MeSH terms

  • Aclarubicin / analogs & derivatives*
  • Aclarubicin / pharmacology*
  • Antibiotics, Antineoplastic / pharmacology*
  • Apoptosis / drug effects*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects*
  • Humans
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / pathology*
  • Proteins / genetics*
  • RNA, Messenger / analysis
  • Time Factors
  • Ubiquitin-Protein Ligases

Substances

  • Antibiotics, Antineoplastic
  • Inhibitor of Apoptosis Proteins
  • Proteins
  • RNA, Messenger
  • aclacinomycins
  • Aclarubicin
  • BIRC2 protein, human
  • Ubiquitin-Protein Ligases