International Journal of Medical Sciences

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20 April 2019

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Int J Med Sci 2018; 15(6):574-579. doi:10.7150/ijms.23285

Research Paper

Salmonella Overcomes Drug Resistance in Tumor through P-glycoprotein Downregulation

Chih-Jen Yang1,2,3, Wen-Wei Chang4,5, Song-Tao Lin6, Man-Chin Chen6, Che-Hsin Lee6,7✉

1. Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan;
2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan;
3. Faculty of Medicine, Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Taiwan;
4. Department of Biomedical Sciences, College of Medical Science and Technology, Chung Shan Medical University, Taichung, Taiwan;
5. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan;
6. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan;
7. Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 404, Taiwan


Chemotherapy is one of effective methods for the treatment of tumor. Patients often develop drug resistance after chemotherapic cycles. Salmonella has potential as antitumor agent. Salmonella used in tandem with chemotherapy had additive effects, providing a rationale for using tumor-targeting Salmonella in combination with conventional chemotherapy. To improve the efficacy and safety of Salmonella, a further understanding of Salmonella interactions with the tumor microenvironment is required. The presence of plasma membrane multidrug resistance protein P-glycoprotein (P-gp) is highly relevant for the success of chemotherapy. Following Salmonella infection, dose-dependent downregulation of P-gp expressions were examined. Salmonella significantly decreased the efflux capabilities of P-gp, as based on the influx of Rhodamine 123 assay. In addition, Salmonella significant reduced the protein express the expression levels of phosph-protein kinase B (P-AKT), phosph-mammalian targets of rapamycin (P-mTOR), and phosph-p70 ribosomal s6 kinase (P-p70s6K) in tumor cells. The Salmonella-induced downregulation of P-gp was rescued by transfection of cells with active P-AKT. Our results demonstrate that Salmonella in tumor sites leads to decrease the expression of P-gp and enhances the combination of Salmonella and 5-Fluorouracil therapeutic effects.

Keywords: Salmonella, P-glycoprotein, 5-Fluorouracil, tumor, combination therapy

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
How to cite this article:
Yang CJ, Chang WW, Lin ST, Chen MC, Lee CH. Salmonella Overcomes Drug Resistance in Tumor through P-glycoprotein Downregulation. Int J Med Sci 2018; 15(6):574-579. doi:10.7150/ijms.23285. Available from