HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Low HDAC6 Expression is Associated with Poorer Survival in Ovarian Cancer
2.2. Characterisation of a Patient-Derived Cell Model of HGSOC
2.3. HDAC6 Knockdown Significantly Inhibited Cell Proliferation and Migration HGSOC
2.4. Pharmacological Inhibition of HDAC6 Slows the Growth of HGSOC Cells
2.5. HDAC6 Inhibition Did not Affect Responses to Paclitaxel in HGSOC Cells
3. Discussion
4. Materials and Methods
4.1. Patients, Tissue Specimens, and Histopathological Review
4.2. HDAC6 Immunohistochemistry (IHC) and Manual Scoring
4.3. HDAC6 mRNA Meta-Analysis
4.4. Cell Line Culture
4.5. SDS-PAGE and Western Blotting
4.6. Transient Transfection and Treatments
4.7. xCELLigence,
4.8. Immunocytochemistry
4.9. Quantitative Reverse-Transcription PCR (RT-PCR)
4.10. Drug Sensitivity Assay
4.11. Caspase 3/7 Assay
4.12. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Clinical Characteristic | Low HDAC6 | High HDAC6 | Overall |
---|---|---|---|
n = 23 (%) | n = 23 (%) | n = 46 (%) | |
Age (years) | |||
Mean | 54 | 60 | 57 |
Median | 54 | 61 | 59 |
Standard Deviation | 9 | 10 | 10 |
Range | 41–74 | 36–76 | 36–76 |
FIGO Stage | |||
I/II | 1 (4.3%) | 5 (27.7%) | 6 (13%) |
III/IV | 22 (95.7%) | 18 (78.3%) | 40 (87%) |
Grade | |||
Unknown | 1 (4.3%) | 1 (4.3%) | 2 (4.3%) |
Low | 1 (4.3%) | 0 (0%) | 1 (2.2%) |
Intermediate | 8 (34.9%) | 6 (26.1%) | 14 (30.5%) |
High | 13 (56.5%) | 16 (69.6%) | 29 (63%) |
Cytoreduction/Cytoreductive surgery | |||
Unknown | 2 (8.7%) | 0 (0%) | 2 (4.3%) |
sub-Optimal > 1 | 3 (13%) | 7 (30.4%) | 10 (21.8%) |
Optimal ≤ 1 | 18 (78.3%) | 16 (69.6%) | 34 (73.9%) |
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Ali, A.; Zhang, F.; Maguire, A.; Byrne, T.; Weiner-Gorzel, K.; Bridgett, S.; O’Toole, S.; O’Leary, J.; Beggan, C.; Fitzpatrick, P.; et al. HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells. Cancers 2020, 12, 3734. https://doi.org/10.3390/cancers12123734
Ali A, Zhang F, Maguire A, Byrne T, Weiner-Gorzel K, Bridgett S, O’Toole S, O’Leary J, Beggan C, Fitzpatrick P, et al. HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells. Cancers. 2020; 12(12):3734. https://doi.org/10.3390/cancers12123734
Chicago/Turabian StyleAli, Ahlam, Fengyu Zhang, Aaron Maguire, Tara Byrne, Karolina Weiner-Gorzel, Stephen Bridgett, Sharon O’Toole, John O’Leary, Caitlin Beggan, Patricia Fitzpatrick, and et al. 2020. "HDAC6 Degradation Inhibits the Growth of High-Grade Serous Ovarian Cancer Cells" Cancers 12, no. 12: 3734. https://doi.org/10.3390/cancers12123734