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

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY Clinical Epigenetics Pub Date : 2024-08-03 DOI:10.1186/s13148-024-01700-3
Nair Lopes, Sofia Salta, Bianca Troncarelli Flores, Vera Miranda-Gonçalves, Margareta P. Correia, Davide Gigliano, Rita Guimarães, Rui Henrique, Carmen Jerónimo
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Abstract

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. 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. 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.
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帕诺比诺司他在食管腺癌和鳞癌细胞系中的抗肿瘤活性
食道癌仍然是一种具有挑战性的疾病,死亡率高,治疗方案少。鉴于这些困难,表观遗传药物已成为患者治疗的潜在替代方案。帕诺比诺司他是一种已被批准用于治疗多发性骨髓瘤患者的 HDAC(组蛋白去乙酰化酶)抑制剂,本研究的目的是评估帕诺比诺司他在正常和恶性食管细胞系中的治疗效果和生物学后果,后者代表了两种主要的组织学亚型:腺癌和鳞癌。帕诺比诺司他能抑制食道癌细胞的生长,阻碍其增殖、集落形成和侵袭。在HDAC组织表达方面,与肿瘤组织相比,正常食管上皮细胞中的HDAC1明显上调,而与非恶性粘膜相比,食管癌中的HDAC3过度表达。正常组织和肿瘤组织的 HDAC2 和 HDAC8 表达没有差异。暴露于帕诺比诺司他(Panobinostat)可有效抑制食道癌细胞的恶性特征。由于HDAC3在食道癌样本中过度表达,这种表观遗传药物可能是食道癌患者的另一种治疗选择。
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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