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帕比司他对食管腺癌和鳞癌细胞系的抗肿瘤活性。

Anti-tumour activity of Panobinostat in oesophageal adenocarcinoma and squamous cell carcinoma cell lines.

机构信息

Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP) - CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Research Center-LAB 3, F Bdg, 1st Floor, Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.

Doctoral Program in Pathology and Molecular Genetics, ICBAS - School of Medicine and Biomedical Sciences - University of Porto (ICBAS-UP), Rua de Jorge Viterbo Ferreira, 228, 4050-313, Porto, Portugal.

出版信息

Clin Epigenetics. 2024 Aug 3;16(1):102. doi: 10.1186/s13148-024-01700-3.

DOI:10.1186/s13148-024-01700-3
PMID:39097736
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11297794/
Abstract

BACKGROUND

Oesophageal cancer remains a challenging disease with high mortality rates and few therapeutic options. In view of these difficulties, epigenetic drugs have emerged as potential alternatives for patient care. The goal of this study was to evaluate the effect and biological consequences of Panobinostat treatment, an HDAC (histone deacetylase) inhibitor already approved for treatment of patients with multiple myeloma, in oesophageal cell lines of normal and malignant origin, with the latter being representative of the two main histological subtypes: adenocarcinoma and squamous cell carcinoma.

RESULTS

Panobinostat treatment inhibited growth and hindered proliferation, colony formation and invasion of oesophageal cancer cells. Considering HDAC tissue expression, HDAC1 was significantly upregulated in normal oesophageal epithelium in comparison with tumour tissue, whereas HDAC3 was overexpressed in oesophageal cancer compared to non-malignant mucosa. No differences between normal and tumour tissue were observed for HDAC2 and HDAC8 expression.

CONCLUSIONS

Panobinostat exposure effectively impaired malignant features of oesophageal cancer cells. Because HDAC3 was shown to be overexpressed in oesophageal tumour samples, this epigenetic drug may represent an alternative therapeutic option for oesophageal cancer patients.

摘要

背景

食管癌仍然是一种具有高死亡率和治疗选择有限的挑战性疾病。鉴于这些困难，表观遗传药物已成为患者治疗的潜在选择。本研究的目的是评估 Panobinostat 治疗的效果和生物学后果，Panobinostat 是一种已被批准用于治疗多发性骨髓瘤患者的组蛋白去乙酰化酶（HDAC）抑制剂，在正常和恶性来源的食管细胞系中进行评估，后者代表两种主要的组织学亚型：腺癌和鳞状细胞癌。

结果

Panobinostat 治疗抑制了食管癌细胞的生长和增殖、集落形成和侵袭。考虑到 HDAC 的组织表达，与肿瘤组织相比，正常食管上皮中 HDAC1 的表达显著上调，而与非恶性黏膜相比，HDAC3 在食管癌中过度表达。HDAC2 和 HDAC8 的表达在正常组织和肿瘤组织之间没有差异。

结论

Panobinostat 暴露有效地损害了食管癌细胞的恶性特征。由于在食管肿瘤样本中观察到 HDAC3 过表达，这种表观遗传药物可能代表食管癌症患者的另一种治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/054a13c01a00/13148_2024_1700_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/de315a46464d/13148_2024_1700_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/e395960f703e/13148_2024_1700_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/f70a0ae4b876/13148_2024_1700_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/cb6b3e9b395d/13148_2024_1700_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/df545870864c/13148_2024_1700_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/888543617391/13148_2024_1700_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/f9c038ebf990/13148_2024_1700_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/054a13c01a00/13148_2024_1700_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/de315a46464d/13148_2024_1700_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/e395960f703e/13148_2024_1700_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/f70a0ae4b876/13148_2024_1700_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/a8284e8f02d2/13148_2024_1700_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/cb6b3e9b395d/13148_2024_1700_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/df545870864c/13148_2024_1700_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/888543617391/13148_2024_1700_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/f9c038ebf990/13148_2024_1700_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7309/11297794/054a13c01a00/13148_2024_1700_Fig9_HTML.jpg

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