Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45alpha expression.
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.
Yang
Cao
C
Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA 02114, USA.
Yang
Shuhua
S
Wood
Kirkham B
KB
Hornicek
Francis J
FJ
Schwab
Joseph H
JH
Fondren
Gertrude
G
Mankin
Henry
H
Duan
Zhenfeng
Z
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D000097642:GADD45 Proteins
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins