Dihydroartemisinin suppresses cancer-associated fibroblast-mediated tumor angiogenesis and lymphangiogenesis in hypopharyngeal squamous cell carcinoma
10.16066/j.1672-7002.2025.06.001
- VernacularTitle:双氢青蒿素抑制下咽鳞状细胞癌相关成纤维细胞促进肿瘤血管和淋巴管生成作用的研究
- Author:
Lanzhen CUI
1
;
Cong XU
;
Xiaoxiao LIU
;
Jing BAI
;
Lijun ZHANG
;
Yu PENG
;
Xiaoming LI
Author Information
1. 联勤保障部队第九八○医院(白求恩国际和平医院)耳鼻咽喉头颈外科,河北 石家庄 050051
- Keywords:
Hypopharyngeal Neoplasms;
Carcinoma,Squamous Cell;
cancer-associated fibroblasts;
signal transducer and activator of transcription 3 pathway;
dihydroartemisinin
- From:
Chinese Archives of Otolaryngology-Head and Neck Surgery
2025;32(6):341-347
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the effects of dihydroartemisinin(DHA)on the functions of cancer-associated fibroblasts(CAFs)in the tumor microenvironment in hypopharyngeal squamous cell carcinoma(HPSCC).METHODS The influence of conditioned media from CAFs and normal fibroblasts(NFs)on tube formation was assessed using a tube formation assay.Secreted protein levels of IL-6,VEGFA,and VEGFC were measured by immunofluorescence and ELISA.Western blotting was used to evaluate the expression of α-SMA,p-STAT3,STAT3,VEGF-A,and VEGF-C within the STAT3 signaling pathway.After treatment with DHA,the optimal concentration for DHA's effect was determined using CCK8 assays and morphological observations of cells.The impact of DHA on angiogenesis was analyzed through tube formation assays,changes in IL-6 expression were detected using ELISA and immunofluorescence,and alterations in α-SMA,p-STAT3,and STAT3 expression were examined by Western blot.RESULTS Both CAFs and NFs exhibited pro-angiogenic and pro-lymphangiogenic effects,with CAFs showing a more pronounced impact.Activated CAFs overexpressed and secreted high levels of IL-6,VEGF-A,and VEGF-C.The concentration of IL-6 in the conditioned medium supernatants of CAF1 and CAF2 was significantly higher than that of NF1 and NF2(P1<0.001,P2<0.05).Similarly,the concentration of VEGF-A was significantly increased(P1<0.05,P2<0.01),and the concentration of VEGF-C was also significantly increased(P1<0.05,P2<0.01).Treatment with DHA inhibited the activated state of CAFs,reducing the expression and secretion of IL-6 and p-STAT3,thereby suppressing tube formation.CONCLUSION Our findings indicate that CAFs promote angiogenesis and lymphangiogenesis in HPSCC via activation of the STAT3 pathway.DHA effectively inhibits this process,suggesting a potential new therapeutic strategy for the treatment of HPSCC.
