Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1
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Jian-Hui Chen
Abstract
Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to −100 and −166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.
Acknowledgments
This research was supported by Huai’an City Science and Technology Support Program (Social Development) Grant NO. HAS2015013-4.
References
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Reviews
- Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours
- The cancer cell adhesion resistome: mechanisms, targeting and translational approaches
- Research Articles/Short Communications
- Protein Structure and Function
- Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios
- Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis
- Molecular Medicine
- Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer
- Cell Biology and Signaling
- Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?
- Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1
- Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide
- Erratum
- Erratum to: Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families
Artikel in diesem Heft
- Frontmatter
- Reviews
- Proteases and cytokines as mediators of interactions between cancer and stromal cells in tumours
- The cancer cell adhesion resistome: mechanisms, targeting and translational approaches
- Research Articles/Short Communications
- Protein Structure and Function
- Mitochondrial cytochrome c oxidase is inhibited by ATP only at very high ATP/ADP ratios
- Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis
- Molecular Medicine
- Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer
- Cell Biology and Signaling
- Is N,N-dimethylglycine N-oxide a choline and betaine metabolite?
- Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1
- Intra- or extra-exosomal secretion of HDGF isoforms: the extraordinary function of the HDGF-A N-terminal peptide
- Erratum
- Erratum to: Tropane alkaloids as substrates and inhibitors of human organic cation transporters of the SLC22 (OCT) and the SLC47 (MATE) families