[The effects of Mcl-1 gene on ATRA-resistant HL-60 cell]

Zhonghua Xue Ye Xue Za Zhi. 2005 Jun;26(6):352-4.
[Article in Chinese]

Abstract

Objective: To investigate the role of Mcl-1 gene in resistance of all-trans retinoic acid (ATRA) of leukemia cells.

Methods: Long-term, intermittent and repetitive exposure of HL-60 cells to ATRA was used to establish a multidrug-resistance cell line (HL-60/ATRA). HL-60/ATRA cells were transfected with Mcl-1 small interference RNA (siRNA) by Lipofectamine 2000. Western blot was used to detect the expression of Mcl-1. The proliferation, apoptosis and differentiation were evaluated by MTT assay, in situ nick end-labeling (TUNEL) and NBT assay, respectively.

Results: The HL-60/ATRA could keep its undifferentiated and proliferative status to a high concentration of ATRA (100 nmol/L) with highly expressed Mcl-1 protein (relative grey scale 0.624 +/- 0.127). Mcl-1 gene knockdown by siRNA (relative grey scale 0.267 +/- 0.086) could reverse the resistance of ATRA of HL-60/ATRA by inhibiting proliferation, and inducing differentiation and apoptosis [apoptosis rate (18.5 +/- 4.5)%].

Conclusion: Mcl-1 gene might be involved in ATRA resistance in HL-60 cells and inhibiting its expression could be a new approach to ATRA resistance reversion.

Publication types

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

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / genetics*
  • HL-60 Cells / drug effects
  • HL-60 Cells / metabolism
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Small Interfering*
  • Tretinoin / pharmacology*

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • Tretinoin