[Mechanism of bortezomib in inducing apoptosis and improving chemosensitivity of Ishikawa cells]

Nan Fang Yi Ke Da Xue Xue Bao. 2010 Jun;30(6):1301-3, 1309.
[Article in Chinese]

Abstract

Objective: To investigate the effect of bortezomib on the apoptosis and drug sensitivity of endometrial cancer cell line Ishikawa cells.

Methods: The IC50 of bortizomib, ADR, DDP and PTX in Ishikawa cells was determined using MTT method. After treatment with IC50 bortezomib for 6 and 12 h, the expressions of caspases-3, caspases-9 and bcl-2 genes were detected by RT-PCR, and the cell apoptotic rate and ROS level Ishikawa cells were evaluated by flow cytometry after treatment with half of the IC50 of the drugs for 24 h.

Results: The IC50 of bortizomib, ADR, DDP, and PTX was 71.6 nmol/L, 0.572 micromol/L, 67.4 micromol/L and 719.5 nmol/L, respectively. Bortizomib significantly increased the mRNA expressions of caspases-3 and caspases-9 but decreased the expression of bcl-2. Compared with the treatment with agents alone, combined treatment of the cells significantly improved the cytotoxicity of the chemotherapeutic agents (P<0.05) and increased the ROS level and the apoptosis of the cells.

Conclusion: Bortizomib can inhibit the protein kinase to induce the apoptosis and enhance the chemosensitivity of Ishikawa cells.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects*
  • Boronic Acids / pharmacology*
  • Bortezomib
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Drug Synergism
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Protease Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Pyrazines / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Boronic Acids
  • Protease Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Pyrazines
  • Reactive Oxygen Species
  • Bortezomib
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9