Sodium butyrate increases P-gp expression in lung cancer by upregulation of STAT3 and mRNA stabilization of ABCB1

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 ABCB1 mRNA stability. This study indicated that we should pay more attention to HDACIs during cancer clinical therapy. Correspondence to Bao-Long Wang, PhD, Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical University, Hefei 230000, China Tel: +86 551 6228 3571; e-mail: wbl196555@163.com Correspondence to Hao Wang, PhD, Department of Clinical Laboratory, Anhui Provincial Hospital, Anhui Medical University, Hefei 230000, China Tel: +86 551 6228 2393; e-mail: wanghao986118@163.com Received July 19, 2017 Accepted December 9, 2017 Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.

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