Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45α expression

作者：Yang, Cao; Yang, Shuhua; Wood, Kirkham B.; Hornicek, Francis J.; Schwab, Joseph H.; Fondren, Gertrude; Mankin, Henry; Duan, Zhenfeng^*

来源：Apoptosis, 2009, 14(1): 124-133.

DOI：10.1007/s10495-008-0282-x

• GADD45 alpha
• Multidrug resistance
• Osteosarcoma
• Apoptosis

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 GADD45 alpha was significantly induced in U-2 OS cells after exposure to paclitaxel (P < 0.0001). However, the induction of GADD45 alpha did not occur in U-2 OS MR cells. Subsequent analysis by Western blot confirmed that the expression of GADD45 alpha 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 GADD45 alpha 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 GADD45 alpha may play a role in drug-induced apoptosis, as well as multidrug resistance in osteosarcoma cells.

• 出版日期2009-1
• 单位华中科技大学