中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (5): 361-367.doi: 10.19401/j.cnki.1007-3639.2021.05.001

• 专题论著 • 上一篇    下一篇

缺氧诱导食管鳞癌细胞中白细胞介素-7表达促进肿瘤进展

陈 杰,王 嫣,张维敏,赵 笛,张凌瑗,詹启敏   

  1. 北京大学肿瘤医院暨北京市肿瘤防治研究所分子肿瘤学研究室,恶性肿瘤发病机制及转化研究教育部重点实验室,北京 100142
  • 出版日期:2021-05-30 发布日期:2021-05-31
  • 通信作者: 詹启敏 E-mail: zhanqimin@bjmu.edu.cn
  • 基金资助:
    国家自然科学基金(81830086,81988101,81772504,81972243)。

Hypoxia induces expression of IL-7 in esophageal squamous cell carcinoma to promote tumor progression 

CHEN Jie, WANG Yan, ZHANG Weimin, ZHAO Di, ZHANG Lingyuan, ZHAN Qimin   

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China
  • Online:2021-05-30 Published:2021-05-31
  • Contact: ZHAN Qimin E-mail: zhanqimin@bjmu.edu.cn

摘要: 背景与目的:缺氧和细胞因子均能介导食管鳞癌(esophageal squamous cell carcinoma,ESCC)的进展,但是相关机制仍未可知。探讨缺氧促进ESCC细胞中白细胞介素-7(interleukin-7,IL-7)分泌增强,进而介导肿瘤进展的机制。法:采用三气培养箱建立缺氧模型,通过ESCC细胞系KYSE410,并采用细胞因子阵列蛋白芯片技术观察缺氧对ESCC中细胞因子分泌的影响。通过KYSE410及KYSE30 ESCC细胞系,采用酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)法观察缺氧对ESCC细胞IL-7分泌的影响。以磷酸盐缓冲液(phosphate-buffered saline,PBS)为对照组,IL-7中和抗体为治疗组,采用MTS法观察IL-7是否能够介导缺氧状态下ESCC细胞增殖。采用transwell实验检测缺氧状态下,IL-7对ESCC细胞侵袭能力的影响。采用信号通路定量ELISA法,检测缺氧通过IL-7对ESCC细胞系中蛋白激酶B(protein kinase B,AKT)活性的影响。结果:缺氧24 h后,KYSE410细胞中多种细胞因子分泌增高,其中以IL-7最为明显。ELISA法进一步证实,缺氧能够显著诱导KYSE410及KYSE30细胞中IL-7分泌增强。MTS法及transwell实验结果显示,IL-7中和抗体能够显著抑制缺氧状态下KYSE410及KYSE30细胞系的增殖及侵袭转移。信号通路ELISA法实验结果显示,IL-7调控缺氧ESCC细胞系中AKT的活性。结论:IL-7是介导缺氧促进ESCC进展的重要细胞因子,本研究为基于IL-7确立ESCC治疗新策略提供了实验依据。

关键词: 食管鳞癌, 缺氧, 白细胞介素-7, 增殖, 侵袭

Abstract: Background and purpose: Hypoxia and cytokines can mediate the malignant progression of esophageal squamous cell carcinoma (ESCC). However, the related mechanism remains unclear. This study aimed to explore the mechanism of hypoxia inducing progression of ESCC via promoting the secretion of interleukin-7 (IL-7). Methods: Three gas incubators were used to establish the hypoxia model, and KYSE410 cells were used to observe the effect of hypoxia on the secretion of cytokines in ESCC. The effect of hypoxia on IL-7 secretion from KYSE410 and KYSE30 cells were observed using enzyme-linked immunosorbent assay (ELISA). Phosphate-buffered saline (PBS) treatment was used as the control group. IL-7 neutralizing antibody was used as the treatment group. The effect of IL-7 on the proliferation of KYSE410 and KYSE30 cells under hypoxic condition was evaluated using MTS assay. The effect of IL-7 on the invasion of indicated ESCC cells under hypoxia was measured using transwell assay. The effect of hypoxia on the activity of protein kinase B (AKT) in indicated ESCC cells was detected by signal pathway quantitative ELISA. Results: Hypoxia promoted the secretion of many cytokines, especially IL-7, in KYSE410 cells after 24 hours incubation. ELISA further confirmed that hypoxia could significantly induce the increase of IL-7 secretion from KYSE410 and KYSE30 cells. MTS and transwell assays showed that IL-7 neutralizing antibody significantly inhibited the proliferation, invasion and migration of KYSE410 and KYSE30 cells under hypoxia. The results of signal pathway ELISA showed that IL-7 regulated AKT activity in ESCC cells. Conclusion: IL-7 is an important cytokine that mediates hypoxia to promote the malignant progression of ESCC, which provides experimental basis for ESCC treatment.

Key words: Esophageal squamous cell carcinoma, Hypoxia, Interleukin-7, Proliferation, Invasion