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丁酸钠对 EBV 相关 T/NK 细胞淋巴瘤的抗肿瘤作用。

Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein-Barr virus-associated T cell and natural killer cell lymphoma.

机构信息

Department of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

出版信息

Cancer Sci. 2014 Jun;105(6):713-22. doi: 10.1111/cas.12418. Epub 2014 May 13.

DOI:10.1111/cas.12418
PMID:24712440
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4317897/
Abstract

The ubiquitous Epstein-Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells. Several EBV-positive and EBV-negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes. Next, EBV-positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi-scid/IL-2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV-associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option.

摘要

普遍存在的 Epstein-Barr 病毒（EBV）不仅感染 B 细胞，还感染 T 细胞和自然杀伤（NK）细胞，并与各种淋巴恶性肿瘤有关。最近的研究报告称，组蛋白去乙酰化酶（HDAC）抑制剂对各种肿瘤细胞具有抗癌作用。在本研究中，我们评估了 HDAC 抑制剂 suberoylanilide hydroxamic acid（SAHA）对 EBV 阳性和 EBV 阴性 T 和 NK 淋巴瘤细胞的体外和体内作用。用不同浓度的 SAHA 处理几种 EBV 阳性和 EBV 阴性的 T 和 NK 细胞系。SAHA 抑制了 T 和 NK 细胞系的增殖，尽管 EBV 阳性和 EBV 阴性细胞系之间没有观察到显著差异。SAHA 在几种 T 和 NK 细胞系中诱导细胞凋亡和/或细胞周期停滞。此外，SAHA 增加了 EBV 裂解基因的表达，降低了 EBV 潜伏基因的表达。接下来，将 EBV 阳性 NK 细胞淋巴瘤细胞皮下接种到严重免疫缺陷的 NOD/Shi-scid/IL-2Rγnull 小鼠中，然后腹腔内给予 SAHA。SAHA 抑制了小鼠异种移植模型中的肿瘤进展和转移。SAHA 通过诱导细胞凋亡或细胞周期停滞对 EBV 相关的 T 和 NK 细胞淋巴瘤显示出明显的抑制作用，可能代表一种替代治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/4317897/39ffd8304f7c/cas0105-0713-f7.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/4317897/39ffd8304f7c/cas0105-0713-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/4317897/6687dedfd43f/cas0105-0713-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/4317897/02b17b0f9f0d/cas0105-0713-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c7a/4317897/c4ac188bda1e/cas0105-0713-f3.jpg
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