Degradation of P-glycoprotein by pristimerin contributes to overcoming ABCB1-mediated chemotherapeutic drug resistance in vitro

Yan,Yan-Yan; Wang,Fang; Zhao,Xiao-Qin; Wang,Xiao-Kun; Chen,Yi-Fan; Liu,Hong; Xie,Yong; Fu,Li-Wu

doi:10.3892/or.2016.5230

Degradation of P-glycoprotein by pristimerin contributes to overcoming ABCB1-mediated chemotherapeutic drug resistance in vitro

Authors:
- Yan-Yan Yan
- Fang Wang
- Xiao-Qin Zhao
- Xiao-Kun Wang
- Yi-Fan Chen
- Hong Liu
- Yong Xie
- Li-Wu Fu
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Affiliations: Institute of Respiratory and Occupational Diseases, Collaborative Innovation Center for Cancer, Shanxi Datong University, Datong, Shanxi 037009, P.R. China, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Cancer Center, Sun Yat-Sen University, Guangzhou, Guangdong 510060, P.R. China
Published online on: November 8, 2016 https://doi.org/10.3892/or.2016.5230
Pages: 31-40
Copyright: © Yan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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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