Artemisinin suppressed tumour growth and induced vascular normalisation in oral squamous cell carcinoma via inhibition of macrophage migration inhibitory factor

青蒿素通过抑制巨噬细胞迁移抑制因子抑制口腔鳞状细胞癌的肿瘤生长并诱导血管正常化

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作者:Xiang-Hua Yu, Jing-Biao Wu, Hua-Yang Fan, Li Dai, Hong-Chun Xian, Bing-Jun Chen, Peng Liao, Mei-Chang Huang, Xin Pang, Mei Zhang, Xin-Hua Liang, Ya-Ling Tang

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.

Conclusion

Artemisinin might induce vascular normalisation and inhibit tumour growth in OSCC through the MIF-signalling pathway.

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.

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