中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
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中国医科大学学报 ›› 2018, Vol. 47 ›› Issue (10): 865-870.doi: 10.12007/j.issn.0258-4646.2018.10.001

• 论著 •    下一篇

APE1通过NF-κB通路调节PD-L1在喉鳞状细胞癌中的表达

杜国强1, 王立银1, 王晓凤2, 李君1, 张明明3, 王瑾1   

  1. 1. 中国医科大学附属盛京医院耳鼻咽喉科, 沈阳 110004;
    2. 中国医科大学附属盛京医院急诊科, 沈阳 110004;
    3. 中国医科大学附属盛京医院病理科, 沈阳 110004
  • 收稿日期:2018-04-10 出版日期:2018-10-30 发布日期:2018-09-30
  • 通讯作者: 王瑾 E-mail:wangj10@sj-hospital.org
  • 作者简介:杜国强(1987-),男,医师,硕士.
  • 基金资助:
    国家自然科学基金青年基金(81202126)

APE1 Regulates the Expression of PD-L1 through the NF-κB Pathway in Laryngeal Squamous Cell Carcinoma

DU Guoqiang1, WANG Liyin1, WANG Xiaofeng2, LI Jun1, ZHANG Mingming3, WANG Jin1   

  1. 1. Otorhinolaryngological Department, Shengjing Hospital, China Medical University, Shenyang 110004, China;
    2. Emergency Department, Shengjing Hospital, China Medical University, Shenyang 110004, China;
    3. Pathology Department, Shengjing Hospital, China Medical University, Shenyang 110004, China
  • Received:2018-04-10 Online:2018-10-30 Published:2018-09-30

摘要: 目的 检测脱嘌呤/脱嘧啶核酸内切酶1(APE1)和程序性死亡蛋白配体1(PD-L1)在喉鳞状细胞癌中的表达,探讨两者的相关性。方法 采用实时定量荧光PCR检测60例喉癌标本及30例癌旁黏膜组织中PD-L1、APE1基因的表达,并分析其与临床病理因素的关系;利用siRNA脂质体转染、脂多糖[LPS,核因子κB(NF-κB)信号通路激动剂]和PDTC(NF-κB信号通路抑制剂)干预Hep-2细胞系,采用Western blotting检测APE1、PD-L1、NF-κB、pNF-κB蛋白的表达。结果 喉癌组织中APE1、PD-L1基因的表达显著高于癌旁组织(P < 0.05) ,两者表达呈正相关(r=0.37,P < 0.01)。PD-L1表达与喉癌发生部位有关,声门型喉癌组织中PD-L1 mRNA表达水平显著高于声门上型和声门下型(P < 0.05)。同时,喉癌组织中APE1 mRNA的表达与淋巴结转移与否具有相关性(P < 0.05)。APE1-siRNA转染Hep-2细胞后,显著抑制细胞APE1、NF-κB、pNF-κB、PD-L1蛋白的表达水平(P < 0.05)。在一定浓度范围内,LPS和PDTC干预Hep-2细胞后,PD-L1、NF-κB蛋白表达分别逐渐增高和逐渐降低(P < 0.05)。而沉默Hep-2细胞中APE1基因表达后进行LPS干预,细胞NF-κB、PD-L1表达较未干预组和LPS干预组降低(P < 0.05)。结论 相对于声门下型和声门上型喉癌,声门型喉癌可能对PD1/PD-L1免疫检查点相关的免疫治疗相对敏感。APE1可能通过NF-κB信号通路调节PD-L1的表达。PD-L1和APE1表达的联合检测对抑制喉癌生长具有潜在的临床价值。

关键词: 喉鳞状细胞癌, 脱嘌呤/脱嘧啶核酸内切酶1, 程序性死亡蛋白配体1, 核因子κB信号通路, Hep-2细胞

Abstract: Objective To investigate the expression and correlation of apurinic/apyrimidinic endonuclease 1 (APE1) and programmed death ligand 1 (PD-L1) in human laryngeal squamous cell carcinoma (LSCC). Methods We collected 60 LSCC tissues and 30 adjacent mucosal tissues and detected expressions of PD-L1 and APE1 and analyzed their correlation with each other and with clinicopathological factors. Hep-2 cells were transfected with siRNA liposomes,lipopolysaccharides[nuclear factor κB (NF-κB) agonists],and PDTC (NF-κB inhibitor). The expressions of APE1,PD-L1,NF-κB,and pNF-κB were detected by Western blotting. Results The expressions of APE1 and PD-L1 mRNA were significantly higher in LSCC tissues than in adjacent tissues (P < 0.05). There was a positive correlation between APE1 and PD-L1 mRNA expressions in LSCC tissues (r=0.37,P < 0.01). The expression of PD-L1 was related to the tumor location,and the level of PD-L1 mRNA was significantly higher in glottic carcinoma than in subglottic and supraglottic carcinomas (P < 0.05). APE1 mRNA expression was associated with lymphatic metastasis (P < 0.05). The levels of APE1,NF-κB,pNF-κB,and PD-L1 were down-regulated in Hep-2 cells transfected by APE1-siRNA (P < 0.05). PD-L1 and NF-κB were increased and decreased after treatment with lipopolysaccharides and PDTC in a certain concentration range,respectively. In APE1-siRNA transfected cells treated with lipopolysaccharides,NF-κB and PD-L1 were down-regulated compared with the control group and the lipopolysaccharide-only group (P < 0.05). Conclusion Compared with subglottic and supraglottic carcinomas,glottic carcinoma may show a better response to PD-1/PD-L1-based immunotherapy. APE1 regulates PD-L1 expression through the NF-κB signaling pathway. Combined determination of PD-L1 and APE1 expressions may have potential clinical significance in inhibiting LSCC growth.

Key words: laryngeal squamous cell carcinoma, apurinic/apyrimidinic endonuclease 1, programmed death ligand 1, nuclear factor-κB pathway, Hep-2 cells

中图分类号: 

  • R767.1
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