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Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin
Wang, Shengpeng1; Wang, Anqi1; Shao, Min2; Lin, Ligen1; Li, Peng1; Wang, Yitao1
2017-08-21
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Abstract

Acquired drug resistance poses a great challenge in cancer therapy. Drug efflux and anti-apoptotic processes are the most two common mechanisms that confer cancer drug resistance. In this study, we found that Schisandrin B (Sch B), one of the major dibenzocyclooctadiene derivatives extracted from Chinese herbal medicine Schisandrae Chinensis Fructus, could significantly enhance the sensitivity of doxorubicin (DOX)-resistant breast cancer and ovarian cancer cells to DOX. Our results showed that Sch B increased the intracellular accumulation of DOX through inhibiting expression and activity of P-glycoprotein (P-gp). Meanwhile, Sch B could markedly downregulate the expression of anti-apoptotic protein survivin. Overexpression of survivin attenuated the sensitizing effects of Sch B, while silencing of survivin enhanced Sch B-mediated sensitizing effects. Furthermore, Sch B preferentially promoted chymotryptic activity of the proteasome in a concentration-dependent manner, and the proteasome inhibitor MG-132 prevented Sch B-induced survivin downregulation. Taken together, our findings suggest that Sch B could be a potential candidate for combating drug resistant cancer via modulating two key factors that responsible for cancer resistance.

DOIhttp://doi.org/10.1038/s41598-017-08817-x
URLView the original
Indexed BySCI
Language英语
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000408106400003
PublisherNATURE PUBLISHING GROUP
The Source to ArticleWOS
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Cited Times [WOS]:8   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLi, Peng; Wang, Yitao
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, 999078, China
2.Department of Bioengineering, Zunyi Medical University Zhuhai Campus, Zhuhai, Guangdong, 519041, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wang, Shengpeng,Wang, Anqi,Shao, Min,et al. Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin[J]. SCIENTIFIC REPORTS,2017,7.
APA Wang, Shengpeng,Wang, Anqi,Shao, Min,Lin, Ligen,Li, Peng,&Wang, Yitao.(2017).Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin.SCIENTIFIC REPORTS,7.
MLA Wang, Shengpeng,et al."Schisandrin B reverses doxorubicin resistance through inhibiting P-glycoprotein and promoting proteasome-mediated degradation of survivin".SCIENTIFIC REPORTS 7(2017).
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