Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45alpha expression

Apoptosis. 2009 Jan;14(1):124-33. doi: 10.1007/s10495-008-0282-x.


To identify apoptosis genes involved in the multidrug resistance of osteosarcoma, a multidrug resistant human osteosarcoma cell line (U-2 OS MR) was established. Apoptosis gene microarray analysis demonstrated that GADD45alpha was significantly induced in U-2 OS cells after exposure to paclitaxel (P < 0.0001). However, the induction of GADD45alpha did not occur in U-2 OS MR cells. Subsequent analysis by Western blot confirmed that the expression of GADD45alpha could be significantly induced by paclitaxel and doxorubicin in U-2 OS cells but not in U-2 OS MR cells. Furthermore, the paclitaxel or doxorubicin treated U-2 OS and KH OS cells have a higher percentage of apoptotic cells when compared with U-2 OS MR and KH OS R2 cells treated with the same drugs. When GADD45alpha was transfected into U-2 OS MR or KH OS R2 and expressed, the cells became more sensitive to chemotherapeutic drugs. These results suggest that GADD45alpha may play a role in drug-induced apoptosis, as well as multidrug resistance in osteosarcoma cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Gene Expression
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Osteosarcoma / metabolism*
  • Time Factors
  • Transfection


  • Antineoplastic Agents
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Nuclear Proteins