帕比司他对食管腺癌和鳞状细胞癌细胞系的抗肿瘤活性。
Anti-tumour activity of Panobinostat in oesophageal adenocarcinoma and squamous cell carcinoma cell lines.
发表日期:2024 Aug 03
作者:
Nair Lopes, Sofia Salta, Bianca Troncarelli Flores, Vera Miranda-Gonçalves, Margareta P Correia, Davide Gigliano, Rita Guimarães, Rui Henrique, Carmen Jerónimo
来源:
Clinical Epigenetics
摘要:
食道癌仍然是一种具有挑战性的疾病,死亡率高,治疗选择很少。鉴于这些困难,表观遗传药物已成为患者护理的潜在替代方案。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 HDAC(组蛋白脱乙酰酶)抑制剂,已被批准用于治疗多发性骨髓瘤患者,在正常和恶性来源的食管细胞系中,后者代表两种主要的组织学亚型:腺癌和鳞状细胞癌。帕比司他治疗抑制食管癌细胞的生长并阻碍其增殖、集落形成和侵袭。考虑到 HDAC 组织表达,与肿瘤组织相比,正常食管上皮中 HDAC1 显着上调,而与非恶性粘膜相比,HDAC3 在食管癌中过度表达。正常组织和肿瘤组织之间的 HDAC2 和 HDAC8 表达没有观察到差异。帕比司他暴露有效削弱了食管癌细胞的恶性特征。由于 HDAC3 在食管肿瘤样本中被证明过度表达,因此这种表观遗传药物可能代表食管癌患者的替代治疗选择。© 2024。作者。
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.© 2024. The Author(s).