CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels

Ru HE; Hongyi JIANG; Chengchi ZHANG; Yuan CHEN; Wenshun LIU; Xinyue DENG; Xiaozheng ZHU; Yunye LIU; Chuanming ZHENG; Yining ZHANG; Chengying SHAO; Yanting DUAN; Jiajie XU

doi:10.1631/jzus.B2400192

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CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels

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Research Article | Updated：2025-04-21

CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels
CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels
CXCL16通过调节GPX1介导的抗氧化水平促进头颈部鳞状细胞癌增殖
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 1, Pages: 92-106(2025)
Affiliations：

1.Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China
2.College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China
3.Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China
4.Department of Postgraduate Education, Jinzhou Medical University, Jinzhou 121000, China
5.The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, China
6.Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou 310014, China
Funds：
DOI：10.1631/jzus.B2400192
CLC：
CSTR：
Received：15 April 2024，

Revised：29 July 2024，

Published Online：30 September 2024，

Published：15 January 2025
Accepted：

何茹,江弘毅,张铖驰等.CXCL16通过调节GPX1介导的抗氧化水平促进头颈部鳞状细胞癌增殖[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(01):92-106.

Ru HE, Hongyi JIANG, Chengchi ZHANG, et al. CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(1): 92-106.
何茹,江弘毅,张铖驰等.CXCL16通过调节GPX1介导的抗氧化水平促进头颈部鳞状细胞癌增殖[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(01):92-106. DOI： 10.1631/jzus.B2400192.

Ru HE, Hongyi JIANG, Chengchi ZHANG, et al. CXCL16 promotes proliferation of head and neck squamous cell carcinoma by regulating GPX1-mediated antioxidant levels[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(1): 92-106. DOI： 10.1631/jzus.B2400192.

摘要

大量研究表明，CXC基序趋化因子配体16（CXCL16）在癌症中的高表达与预后不良以及肿瘤细胞的增殖、迁移和侵袭有关。虽然CXCL16可以作为肿瘤生物标志物，但其调节头颈部鳞状细胞癌（HNSCC）的潜在机制尚不清楚。在本研究中，我们旨在研究CXCL16在HNSCC中的表达，并揭示其潜在的生物学机制。我们在癌症基因组图谱（TCGA）数据库、本中心医院HNSCC患者的组织样本和HNSCC细胞系中均检测到CXCL16的高表达。实验结果表明，CXCL16敲低可抑制HNSCC细胞的增殖、迁移和侵袭。转录组测序显示，CXCL16可能通过调节谷胱甘肽过氧化物酶1（GPX1）的抗氧化途径影响HNSCC细胞生长。si-CXCL16细胞中活性氧（ROS）的水平升高，可能与抑制细胞增殖、迁移和侵袭有关。此外，与si-CXCL16组相比，si-CXCL16和GPX1抑制剂Eldecalcitol（ED-71）协同作用组能显著抑制HNSCC细胞的生长。综上，CXCL16可通过调节GPX1介导的抗氧化途径促进HNSCC细胞的发展。因此，靶向细胞CXCL16表达可能是治疗HNSCC的一个候选策略。

Abstract

Numerous studies have demonstrated that the high expression of CXC motif chemokine ligand 16 (CXCL16) in cancer correlates with poor prognosis

as well as tumor cell proliferation

migration

and invasion. While CXCL16 can serve as a tumor biomarker

the underlying mechanism in modulating head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study

the aimed was to investigate the CXCL16 expression in HNSCC and to uncover the potential underlying mechanism. Hereby

we determined the high expression of CXCL16 in The Cancer Genome Atlas (TCGA) database

as well as in tissue samples from patients with HNSCC at our central hospital and from HNSCC cell lines. The results showed that

CXCL16

knockdown inhibited the proliferation

migration

and invasion of HNSCC cells. Mechanistically

transcriptome sequencing revealed that CXCL16 may affect HNSCC cell growth by regulating the antioxidant pathway of glutathione peroxidase 1 (GPX1). The reactive oxygen species (ROS) levels were elevated in small interfering CXCL16 (si-CXCL16) cells

which may contribute to the inhibition of cell proliferation

migration

and invasion. Moreover

treatment of cells with the GPX1 inhibitor eldecalcitol (ED-71) revealed that HNSCC cell growth was significantly inhibited in the synergistic group of si-CXCL16 and GPX1 inhibitor compared to the si-CXCL16 group. In conclusion

CXCL16 contributed to the development of HNSCC cells by modulating the GPX1-mediated antioxidant pathway. Thus

targeting cellular CXCL16 expression seems to be a promising strategy for treating HNSCC.

关键词

Keywords

references

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