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Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45α expression

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Abstract

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 GADD45α was significantly induced in U-2 OS cells after exposure to paclitaxel (P < 0.0001). However, the induction of GADD45α did not occur in U-2 OS MR cells. Subsequent analysis by Western blot confirmed that the expression of GADD45α 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 GADD45α 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 GADD45α may play a role in drug-induced apoptosis, as well as multidrug resistance in osteosarcoma cells.

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Acknowledgments

Dr. C. Yang is supported through a grant from the Chinese Council of Scholarship. Dr. Z. Duan is supported, in part, through a grant from the National Cancer Institute, NIH (Nanotechnology Platform Partnership), R01-CA119617. Support has also been provided by the Gaetagno and Wechsler funds.

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Correspondence to Zhenfeng Duan.

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Yang, C., Yang, S., Wood, K.B. et al. Multidrug resistant osteosarcoma cell lines exhibit deficiency of GADD45α expression. Apoptosis 14, 124–133 (2009). https://doi.org/10.1007/s10495-008-0282-x

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