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Knockdown of eIF4E suppresses cell growth and migration, enhances chemosensitivity and correlates with increase in Bax/Bcl-2 ratio in triple-negative breast cancer cells

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Abstract

Elevated activity of the eukaryotic translation initiation factor 4E (eIF4E) plays crucial roles in tumorigenesis and disease progression by disproportionately increasing translation of mRNAs coding proteins that play significant roles in all aspects of malignancy, providing that eIF4E as an attractive target for therapeutic intervention. In this study, we showed that inhibition of eIF4E by small interfering RNAs (siRNA) resulted in cell cycle arrest and suppression of colony formation in MDA-MB-231 triple-negative (TN) breast cancer cells. Migration transwell assay revealed that repression of eIF4E effectively inhibited motility of MDA-MB-231 cancer cells. Importantly, we showed that silencing of eIF4E sensitized MDA-MB-231 cells to chemotherapeutic drugs of cisplatin, adriamycin, paclitaxel and docetaxel as assessed by MTT assay. Moreover, Western blot assay showed that eIF4E siRNA increased Bax/Bcl-2 ratio in MDA-MB-231 cells. Taken together, we showed that knockdown of eIF4E suppressed cell growth and migration, enhanced chemosensitivity, suggesting a potential therapeutic target in TN breast carcinoma.

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Abbreviations

eIF4E:

The eukaryotic translation initiation factor 4E

TN:

Triple-negative

ER:

Estrogen receptor

PgR:

Progesterone receptor

PI3K:

Phosphatidylinositol 3-kinase

ODC:

Ornithine decarboxylase

MMP-9:

Matrix metalloproteinase-9

siRNA:

Small interfering RNAs

ADR:

Adriamycin

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Acknowledgments

This research work was supported by Guangdong Province Science & technology Fund (2008B06060029 to LP X) and Major Science and Technology Project of “National significant new drug creation” (2008ZX09312-002 to LP X).

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Authors and Affiliations

  1. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road East, 510060, Guangzhou, China

    Fei-fei Zhou, Min Yan, Gui-fang Guo, Fang Wang, Hui-juan Qiu, Fei-meng Zheng, Yan Zhang, Qiang Liu, Xiao-feng Zhu & Liang-ping Xia

  2. VIP Region, Cancer Center, Sun Yat-Sen University, 651 Dongfeng Road East, 510060, Guangzhou, China

    Fei-fei Zhou, Gui-fang Guo, Fang Wang, Hui-juan Qiu & Liang-ping Xia

  3. Department of Cancer Center, The First People’s Hospital of Foshan, 81 Lingnan Road North, 528000, Foshan, Guangdong, China

    Fei-fei Zhou

Authors
  1. Fei-fei Zhou
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  2. Min Yan
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  3. Gui-fang Guo
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  4. Fang Wang
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  7. Yan Zhang
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  8. Qiang Liu
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  10. Liang-ping Xia
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Corresponding author

Correspondence to Liang-ping Xia.

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Fei-fei Zhou and Min Yan contributed equally to this work.

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Zhou, Ff., Yan, M., Guo, Gf. et al. Knockdown of eIF4E suppresses cell growth and migration, enhances chemosensitivity and correlates with increase in Bax/Bcl-2 ratio in triple-negative breast cancer cells. Med Oncol 28, 1302–1307 (2011). https://doi.org/10.1007/s12032-010-9630-0

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  • DOI: https://doi.org/10.1007/s12032-010-9630-0

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