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Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells

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Abstract

Combined treatment modalities using tumor necrosis factor related apoptosis-inducing ligand L (TRAIL) and cytotoxic drugs revealed highly additive effects in some tumor cell lines. Little is known about the efficacy and underlying mechanistic effects of the modalities in chemoresistant tumor cells. The purpose of this study is to investigate the possible role of JNK in the synergistic effect in Doxorubicin (Adriamycin, ADM) resistant MCF-7/ADM cells. Here we showed that the JNK pathway was activated slightly by TRAIL in MCF-7/ADM cell lines and was enhanced by the combination of the two treatments. Inhibition of JNK activity by transfection with dominant-negative JNK blocks TRAIL plus ADM induced-apoptosis significantly, and selective stimulation of the JNK pathway sensitizes ADM resistant breast cancer cells to ADM and TRAIL co-treatment through activation of mitochondria-regulated apoptotic pathway. We conclude that the JNK pathway plays an important role in mediating TRAIL plus ADM induced-apoptosis in breast cancer cells.

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Abbreviations

JNK:

c-Jun NH2-terminal kinase

TRAIL:

Tumor necrosis factor related apoptosis-inducing ligand

ADM:

Adriamycin

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Authors and Affiliations

  1. Cancer Biology Research Center, Tongji Hospital, Tongji Medical School, Huazhong, University of Science and Technology, 1095 Jiefang Ave., Wuhan, Hubei, 430030, P. R. China

    Fang Li, Li Meng, Hui Xing, Jianfeng Zhou, Shixuan Wang, Lei Huang, Gang Xu, Huaishi Zhu, Yunping Lu & Ding Ma

Authors
  1. Fang Li
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  2. Li Meng
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  3. Hui Xing
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  4. Jianfeng Zhou
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  5. Shixuan Wang
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  6. Lei Huang
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  7. Gang Xu
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  8. Huaishi Zhu
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  9. Yunping Lu
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  10. Ding Ma
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Corresponding author

Correspondence to Ding Ma.

Additional information

Fang Li and Li Meng contributed equally to this work.

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Li, F., Meng, L., Xing, H. et al. Essential role of c-Jun-NH2-terminal kinase on synergy induction of apoptosis by TRAIL plus ADM in ADM resistant MCF-7/ADM cells. Apoptosis 11, 1239–1246 (2006). https://doi.org/10.1007/s10495-006-7494-8

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  • DOI: https://doi.org/10.1007/s10495-006-7494-8

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