DNA 甲基转移酶 1 在与治疗抵抗相关的咽癌中的作用。

Role of DNA methyltransferase 1 in pharyngeal cancer related to treatment resistance.

机构信息

Department of Hematology and Oncology, Chang Gung Memorial Hospital at Chiayi, Taiwan.

出版信息

Head Neck. 2011 Aug;33(8):1132-43. doi: 10.1002/hed.21586. Epub 2011 Jan 31.

DOI:10.1002/hed.21586

PMID:21284050

Abstract

BACKGROUND

The purpose of the present study was to highlight the role of DNA methyltransferase 1 (DNMT1) and its potential for improving treatment and informing prognosis for pharyngeal cancer.

METHODS

Human pharyngeal cancer cell lines FaDu and its derivative FaDu-C225-R were selected for cellular experiments. Furthermore, 95 pharyngeal cancer tissue specimens were analyzed by immunohistochemical staining.

RESULTS

DNMT1 was over-expressed in pharyngeal cancer specimens and cells with activated interleukin (IL)-6 signaling. When DNMT1 activity was blocked, accelerated tumor growth and treatment resistance were overcome as demonstrated by cell culture and animal experiments. The reduction in DNMT1 was associated with increased apoptosis, cell cycle arrest, and augmented irradiation-induced free radical levels and DNA damage. Furthermore, positive staining for DNMT1 in clinical cancer specimens was significantly linked to lower rates of response to treatments and shorter survival of patients with pharyngeal cancer.

CONCLUSION

DNMT1 may be a significant clinical predictor and a potential treatment strategy against head and neck cancer.

摘要

背景

本研究旨在强调 DNA 甲基转移酶 1（DNMT1）的作用及其在改善治疗和预测预后方面的潜力，以用于治疗咽癌。

方法

选择人咽癌细胞系 FaDu 及其衍生的 FaDu-C225-R 进行细胞实验。此外，通过免疫组织化学染色分析了 95 例咽癌组织标本。

结果

DNMT1 在具有激活白细胞介素（IL）-6 信号的咽癌标本和细胞中过度表达。当抑制 DNMT1 活性时，通过细胞培养和动物实验证明可以克服肿瘤生长加速和治疗耐药性。DNMT1 的减少与增加的细胞凋亡、细胞周期停滞以及增强的辐射诱导的自由基水平和 DNA 损伤有关。此外，临床癌症标本中 DNMT1 的阳性染色与咽癌患者对治疗的反应率降低和生存时间缩短显著相关。