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山东大学学报（医学版） ›› 2017, Vol. 55 ›› Issue (4): 65-70.doi: 10.6040/j.issn.1671-7554.0.2016.1467

• 临床医学 • 上一篇    下一篇

肺腺癌中缺氧诱导因子-1α调控程序性死亡因子配体1的表达

张智慧,王丽丽,高华,张健,李娟,李远,武春晓,卢志明   

  1. 山东大学附属省立医院检验部, 山东 济南 250021
  • 收稿日期:2016-11-09 出版日期:2017-04-10 发布日期:2017-04-10
  • 通讯作者: 卢志明. E-mail:luzhiming@sdu.edu.cn E-mail:luzhiming@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(81372775);山东省医药卫生科技发展计划(2014WS0076)

Role of hypoxia-inducible factor-1α in the regulation of programmed death ligand 1 expression in lung adenocarcinoma

ZHANG Zhihui, WANG Lili, GAO Hua, ZHANG Jian, LI Juan, LI Yuan, WU Chunxiao, LU Zhiming   

  1. Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
  • Received:2016-11-09 Online:2017-04-10 Published:2017-04-10

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摘要： 目的 研究缺氧诱导因子-1α(HIF-1α)和程序性死亡因子配体1(PD-L1)在肺腺癌中的表达与临床病理特征的关系,探讨肺腺癌中HIF-1α对PD-L1的调控作用。 方法 应用免疫组织化学方法检测99例肺腺癌组织中HIF-1α、PD-L1的表达。CoCl2模拟化学性缺氧处理肺腺癌细胞,并将其分为正常组及CoCl2组,qRT-PCR检测HIF-1α、PD-L1 mRNA表达,Western blotting检测HIF-1α、PD-L1蛋白表达。siRNA-HIF-1α瞬时转染肺腺癌细胞,并将其分为阴性对照组及siR-HIF-1α组,qRT-PCR、Western blotting检测转染效率及PD-L1 mRNA和蛋白的表达。 结果 99例肺腺癌组织中,HIF-1α和PD-L1的阳性率分别为47.48%和34.34%,HIF-1α表达水平与患者年龄和临床分期有关(P<0.05),PD-L1表达水平与患者临床分期有关(P<0.05),HIF-1α蛋白表达与PD-L1蛋白表达呈正相关(P<0.01)。与正常组相比,CoCl2组细胞中HIF-1α蛋白表达水平明显升高(t=-2.394, P=0.029),PD-L1 mRNA及蛋白表达水平随之明显升高(t=-3.146, P=0.006; t=-3.308, P=0.004)。与阴性对照组相比,siR-HIF-1α组沉默处理细胞后,PD-L1 mRNA及蛋白表达水平显著降低(t=2.746, P=0.014; t=2.339, P=0.033)。 结论 肺腺癌组织中HIF-1α和PD-L1明显共表达;PD-L1表达受HIF-1α调控。

关键词: 程序性死亡因子配体1, 肺腺癌, 缺氧诱导因子-1α

Abstract: Objective To analyze the association of hypoxia-inducible factor-1α(HIF-1α)and programmed death ligand 1(PD-L1)expression and clinicopathologic features in lung adenocarcinoma, and to investigate the potential role of HIF-1α in the regulation of PD-L1 expression. Methods The expressions of HIF-1α and PD-L1 of 99 cases with lung adenocarcinoma were examined by immunohistochemical method. The lung adenocarcinoma cells were treated with hypoxia mimic CoCl2 and divided into normal group and CoCl2 group. The mRNA and protein expressions of HIF-1α and PD-L1 were detected with qRT-PCR and Western blotting, respectively. The lung adenocarcinoma cells were transfected with siRNA-HIF-1α and divided into negative control group and siR-HIF-1α group. The transfection efficiency of siRNAs and the expression of PD-L1 were detected by qRT-PCR and Western blotting, respectively. Results The positive expression rates of HIF-1α and PD-L1 were 47.48% and 34.34% in 99 cases with lung adenocarcinoma, respec- 山 东 大 学 学 报 (医 学 版)55卷4期 -张智慧,等.肺腺癌中缺氧诱导因子-1α调控程序性死亡因子配体1的表达 \=-tively. The expression of HIF-1α was correlated with age and clinical stage(P<0.05). The expression of PD-L1 was correlated with clinical stage(P<0.05). The expressions of HIF-1α and PD-L1 were positive correlated(P<0.01). Compared with the normal group, the protein expression of HIF-1α significantly increased(t=-2.394, P=0.029), and the mRNA and protein expressions of PD-L1 increased subsequently in the CoCl2 group(t=-3.146, P=0.006; t=-3.308, P=0.004). Compared with the negative control group, the mRNA and protein expressions of PD-L1 decreased dramatically in the siR-HIF-1α group(t=2.746, P=0.014; t=2.339, P=0.033). Conclusion The HIF-1α and PD-L1 proteins are highly co-expressed, and HIF-1α can up-regulate the expression of PD-L1 in lung adenocarcinoma.

Key words: Hypoxia-inducible factor-1α, Programmed death ligand 1, Lung adenocarcinoma

中图分类号: 

  • R734.2
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