靶向抑制高表达HRR蛋白增强肿瘤细胞对放化疗的敏感性

doi:10.3969/j.issn.1673-8640.2018.07.019

检验医学 ›› 2018, Vol. 33 ›› Issue (7): 657-662.DOI: 10.3969/j.issn.1673-8640.2018.07.019

靶向抑制高表达HRR蛋白增强肿瘤细胞对放化疗的敏感性

朱佳蓓¹, 黄楠², 崔中奇², 杨庆源², 潘秋辉¹

1.上海交通大学医学院附属上海儿童医学中心检验科,上海 200127
2.同济大学附属上海第十人民医院检验科,上海 200072

收稿日期:2017-05-15 出版日期:2018-07-30 发布日期:2018-07-27
作者简介:null
作者简介：朱佳蓓,女,1994年生,学士,主要从事DNA损伤在肿瘤治疗中的应用、机制研究。
基金资助:
国家自然科学基金项目（81371913、81572330）

Targeting inhibition on the overexpressed HRR proteins in cancer cells to enhance chemoradio-sensitivity

ZHU Jiabei¹, HUANG Nan², CUI Zhongqi², YANG Qingyuan², PAN Qiuhui¹

1. Department of Clinical Laboratory,Shanghai Children's Medical Center,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China
2. Department of Clinical Laboratory,Shanghai Tenth People's Hospital,Tongji University,Shanghai 200072,China

Received:2017-05-15 Online:2018-07-30 Published:2018-07-27

摘要/Abstract

摘要：

同源重组修复（HRR）主要通过修复哺乳动物细胞中外源或内源性的DNA双链断裂,维持正常细胞基因组的完整性与稳定性,从而阻止细胞癌变。有研究发现高表达HRR蛋白的肿瘤细胞具有较强的损伤修复活力,通过修复放化疗诱导的DNA损伤,抑制凋亡途径以及活化细胞增殖信号通路,使其对放化疗产生耐受性,肿瘤细胞得以存活。这类HRR蛋白在肿瘤细胞中起到了癌基因的功效,维持了肿瘤细胞基因组的稳定性,促进了肿瘤的发生、发展,因而肿瘤细胞中高表达的HRR蛋白成为了肿瘤精准化治疗的潜在靶点。通过药物诱导HRR蛋白过度表达不仅能促进肿瘤细胞的凋亡,而且可以进一步提高肿瘤细胞对放化疗的敏感性。

关键词: 同源重组修复蛋白, 癌基因, 肿瘤治疗

Abstract:

Homologous recombination repair （HRR） is a prominent approach for repairing exogenous and endogenous DNA double-stranded breaks in mammalian cells,which can preserve genome integrity and stability to ensure the function and viability of mammalian cells. It has been widely recognized as a tumor suppressor. Recent studies have found that cancer cells with increased expression of HRR proteins hold powerful repair vitality,causing resistance to chemotherapies and radiotherapies by repairing DNA damage triggered by these curing methods,impeding cell apoptosis pathway and activating cell survival pathway,thus greatly promoting cancer cell survival. These overexpressed proteins play an oncogenic role in cancer cells,as indicate by maintaining genome stability of these cells and promoting tumorigenesis and tumor development,thereby providing potential targets of precision cancer therapy. Targeting inhibition through drugs on the overexpressed HRR proteins in cancer cells will not only stimulate cell apoptosis,but also remarkably enhance the cellular sensitivity to ionizing radiation and cytotoxic chemotherapies.

Key words: Homologous recombination repair protein, Oncogene, Tumor therapy

中图分类号:

R446.62

朱佳蓓, 黄楠, 崔中奇, 杨庆源, 潘秋辉. 靶向抑制高表达HRR蛋白增强肿瘤细胞对放化疗的敏感性[J]. 检验医学, 2018, 33(7): 657-662.

ZHU Jiabei, HUANG Nan, CUI Zhongqi, YANG Qingyuan, PAN Qiuhui. Targeting inhibition on the overexpressed HRR proteins in cancer cells to enhance chemoradio-sensitivity[J]. Laboratory Medicine, 2018, 33(7): 657-662.

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靶向抑制高表达HRR蛋白增强肿瘤细胞对放化疗的敏感性

Targeting inhibition on the overexpressed HRR proteins in cancer cells to enhance chemoradio-sensitivity

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