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Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1
- Source :
- Anti-Cancer Drugs; March 2018, Vol. 29 Issue: 3 p227-233, 7p
- Publication Year :
- 2018
-
Abstract
- As a new type of anticancer drug, the effect of histone deacetylase inhibitors (HDACIs) in cancer clinical therapy is disappointing owing to drug resistance. P-glycoprotein (P-gp) is clearly recognized as a multidrug resistance protein. However, the relationship between P-gp and sodium butyrate (SB), a kind of HDACIs, has not been investigated. In this study, we found that SB increased mRNA and protein expression of P-gp in lung cancer cells and the underlying mechanisms were elucidated. We found that SB treatment enhanced the mRNA and protein expression of STAT3 rather than that of β-catenin, Foxo3a, PXR, or CAR, which were reported to directly regulate the transcription of ABCB1, a P-gp-encoding gene. Interestingly, inhibition of STAT3 expression obviously attenuated SB-increased P-gp expression in lung cancer cells, indicating that STAT3 played an important role in SB-mediated P-gp upregulation. Furthermore, we found that SB increased the mRNA stability of ABCB1. In summary, this study showed that SB increased P-gp expression by facilitating transcriptional activation and improving ABCB1mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy.
Details
- Language :
- English
- ISSN :
- 09594973 and 14735741
- Volume :
- 29
- Issue :
- 3
- Database :
- Supplemental Index
- Journal :
- Anti-Cancer Drugs
- Publication Type :
- Periodical
- Accession number :
- ejs48602120
- Full Text :
- https://doi.org/10.1097/CAD.0000000000000588