Journal
ONCOLOGY REPORTS
Volume 37, Issue 1, Pages 31-40Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2016.5230
Keywords
pristimerin; ABCB1; P-glycoprotein; multidrug resistance; protein degradation
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Funding
- National Science Foundation for Young Scientists of Shanxi Province [2014021037-6]
- Research Foundation of Collaborative Innovation Center for Cancer
- Priming Scientific Research Foundation [2010-B-11]
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ABCB1 (P-glycoprotein, ABCB1/MDR1) is one of the major members of the ABC transporters linked to MDR in cancer cells. In this study, we observed that pristimerin, a natural triterpenoid, potently decreased P-gp in a dose dependent manner in both drug-resistant KBv200 and stable transfected HEK293/ABCB1 cell lines. Moreover, pristimerin also inhibited cell proliferation and induced apoptosis in both cell lines. Intriguingly, reverse transcription-PCR, real-time PCR and protein turn-over assay revealed that the decrease of P-gp was independent of mRNA level but primarily owing to its protein stability. Furthermore, immunofluorescence study with anti-P-gp antibody showed that pristimerin disturbed the subcellular distribution of P-gp with decreased location in the plasma membrane. Taken together, these data suggest that subcellular distribution of P-gp and subsequent downregulation by pristimerin contribute to overcoming ABCB1-mediated chemotherapeutic drug resistance. Our findings suggested inducing the decrease of P-gp membrane protein could be a new promising alternative therapeutic strategy in ABCB1-mediated MDR.
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