[Inhibition effect of fludarabine on the growth of myelodysplastic syndrome cell line MUTZ-1 and its mechanism]

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2006 Mar;35(2):136-42. doi: 10.3785/j.issn.1008-9292.2006.02.005.
[Article in Chinese]

Abstract

Objective: To investigate the inhibition effect of fludarabine on the growth of human MDS-RAEB cell line MUTZ-1 and to explore the possible cellular and molecular mechanism.

Methods: The apoptosis of MUTZ-1 cells induced by fludarabine was studied by transmission electron microscope, MTT assay, DNA ladder test, flow cytometry and RT-PCR method.

Result: Treatment with fludarabine remarkably inhibited the growth of MUTZ-1 cells, the 24 h IC(50), 48 h IC(50) and 72 h IC(50) of fludarabine for MUTZ-1 cells were 137.65 mg/L, 6.27 mg/L and 0.51 mg/L, respectively. Fludarabine inhibited the growth of MUTZ-1 cells in a dose-dependent and time-dependent manner. After treated by fludarabine (1 mg/L-16 mg/L)for 24 h, MUTZ-1 cells showed the typical features of apoptosis. After fludarabine treatment the mRNA expression of Bcl-2, Bax, survivin, XIAP, cIAP-1 and cIAP-2 was not changed, but the mitochondrial membrane potential (MMP) was decreased.

Conclusion: With a certain range of dose fludarabine (1 mg/L-16 mg/L)could inhibit MUTZ-1 cell growth by inducing cells apoptosis. MMP may play a certain role in apoptosis of MUTZ-1 cells induced by fludarabine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / biosynthesis
  • Microtubule-Associated Proteins / genetics
  • Myelodysplastic Syndromes / pathology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Survivin
  • Vidarabine / analogs & derivatives*
  • Vidarabine / pharmacology
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Survivin
  • bcl-2-Associated X Protein
  • Vidarabine
  • fludarabine