HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple-negative breast cancer cells
| العنوان: | HDAC6 inhibition enhances the anti-tumor effect of eribulin through tubulin acetylation in triple-negative breast cancer cells |
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| المؤلفون: | Yoshie Hasegawa, Takeshi Uehara, Takaaki Oba, Mayu Ono, Hisanori Matoba, Ken-ichi Ito |
| المصدر: | Breast Cancer Research and Treatment. 186:37-51 |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Combination therapy, Triple Negative Breast Neoplasms, Histone Deacetylase 6, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Tubulin, Cell Line, Tumor, medicine, Humans, Furans, skin and connective tissue diseases, Vorinostat, Triple-negative breast cancer, Cell Proliferation, Acetylation, Ketones, medicine.disease, Blot, 030104 developmental biology, Oncology, chemistry, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Eribulin, medicine.drug |
| الوصف: | Improved prognosis for triple-negative breast cancer (TNBC) has plateaued and the development of novel therapeutic strategies is required. This study aimed to explore the anti-tumor effect of combined eribulin and HDAC inhibitor (vorinostat: VOR, pan-HDAC inhibitor and ricolinostat: RICO, selective HDAC6 inhibitor) treatment for TNBC. The effect of eribulin in combination with an HDAC inhibitor was tested in three TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157) and their eribulin-resistant derivatives. The expression of acetylated α-tubulin was analyzed by Western blotting for TNBC cells and immunohistochemical analyses for clinical specimens obtained from breast cancer patients who were treated with eribulin. The simultaneous administration of low concentrations (0.2 μM) of VOR or RICO enhanced the anti-tumor effect of eribulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. Meanwhile, pretreatment with 5 μM of VOR or RICO enhanced eribulin sensitivity in all three cell lines. Low concentration of VOR or RICO increased acetylated α-tubulin expression in MDA-MB-231 and Hs578T cells. In contrast, whereas 5 μM of VOR or RICO increased the expression of acetylated α-tubulin in MDA-MB-157 cells, low concentrations did not. Eribulin increased the expression of acetylated α-tubulin in MDA-MB-231 and Hs578T cells but not in MDA-MB-157 cells. These phenomena were also observed in eribulin-resistant cells. Immunohistochemical analyses revealed that the expression of acetylated α-tubulin was increased after eribulin treatment in TNBC. HDAC6 inhibition enhances the anti-tumor effect of eribulin through the acetylation of α-tubulin. This combination therapy could represent a novel therapeutic strategy for TNBC. |
| تدمد: | 1573-7217 0167-6806 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::98c3966e9c68d483bd5e168618044530 https://doi.org/10.1007/s10549-020-06033-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....98c3966e9c68d483bd5e168618044530 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 15737217 01676806 |
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