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Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR pathway

Gene Therapy volume 21, pages 309–316 (2014)Cite this article

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Abstract

Salmonella have been demonstrated to inhibit tumor growth. However, the mechanism of Salmonella-induced tumor cell death is less defined. Autophagy is a cellular process that mediates the degradation of long-lived proteins and unwanted organelles in the cytosol. Tumor cells frequently display lower levels of basal autophagic activity than their normal counterparts and fail to increase autophagic activity in response to stresses. Autophagy is involved in the cell defense elimination of bacteria. The signaling pathways leading to activation of Salmonella-induced autophagy in tumor cells remain to be elucidated. We used autophagy inhibitor (3-Methyladenine) and apoptosis inhibitor (Z-VAD-FMK) to demonstrate that Salmonella may induce cell death via apoptosis and autophagic pathway. Meanwhile, we suggested that Salmonella induce autophagy in a dose- and time-dependent manner. The autophagic markers were increased after tumor cell infected with Salmonella. In addition, the protein express levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells were decreased by western analysis after Salmonella infection. In conclusion, our results point out that Salmonella induce the autophagic signaling pathway via downregulation of AKT/mTOR pathway. Herein, our findings that Salmonella in controlling tumor growth may induce autophagic signal pathway.

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Acknowledgements

This work was supported by National Science Council from Taiwan (NSC101-2320-B039-012-MY3) and China Medical University (CMU102-S-29). We are grateful for the technical assistance of Electron Microscope Laboratory of Tzong Jwo Tang, School of Medicine, Fu Jen Catholic University.

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Authors and Affiliations

  1. Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan

    C-H Lee & J-J Liu

  2. Graduate Institute of Basic Medical Science, School of Medicine, China Medical University, Taichung, Taiwan

    C-H Lee & S-T Lin

  3. Department of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan

    W-W Chang

  4. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

    W-W Chang

  5. Department of Nursing, Chung Hwa University of Medical Technology, Tainan, Taiwan

    J-L Hsieh

  6. Department of Environmental Engineering and Science, Feng Chia University, Taichung, Taiwan

    W-K Wang

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  1. C-H Lee
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Correspondence to C-H Lee.

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Lee, CH., Lin, ST., Liu, JJ. et al. Salmonella induce autophagy in melanoma by the downregulation of AKT/mTOR pathway. Gene Ther 21, 309–316 (2014). https://doi.org/10.1038/gt.2013.86

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