Effect of JAK2/STAT3 pathway on chemotherapy sensitivity in head and neck squamous cell carcinoma
10.12354/j.issn.1000-8179.2024.20240868
- VernacularTitle:JAK2/STAT3信号通路对头颈部鳞状细胞癌化疗敏感性的影响
- Author:
Sun MENGYU
1
,
2
;
Liu CHAO
;
Xing BOFAN
;
Wu HAN
;
Ren YU
;
Zhou XUAN
Author Information
1. 天津医科大学肿瘤医院颌面耳鼻喉肿瘤科,国家恶性肿瘤临床医学研究中心,天津市"肿瘤防治"重点实验室,天津市恶性肿瘤临床医学研究中心(天津市 300060)
2. 天津市头颈部肿瘤基础医学与转化医学重点实验室,药物成药性评价与系统转化全国重点实验室
- Keywords:
head and neck squamous cell carcinoma(HNSCC);
Janus kinase 2(JAK2);
signal transducer and activator of transcription 3(STAT3);
chemotherapy sensitivity
- From:
Chinese Journal of Clinical Oncology
2024;51(19):1009-1015
- CountryChina
- Language:Chinese
-
Abstract:
Objective:We examined the levels of Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling in head and neck squamous cell carcinoma(HNSCC)and their influence on chemotherapy sensitization.Methods:Sixty patients with HNSCC who were treated at Tianjin Medical University Cancer Institute&Hospital,between January 2018 and December 2022,were included in the study.Levels of expressed JAK2,p-STAT3Y705,c-Myc,and Ki-67 in HNSCC tissues were evaluated using immunohistochemical staining,and correlation analysis was performed.The viability of UM-SCC1 cells treated with fedratinib,a JAK2 inhibitor,combined with cisplatin(DDP)and paclitaxel(PTX)was determined using the CCK8 assay.Western blot was performed to detect p-STAT3Y705 expression in tumor tissues and HNSCC cell lines.SCC15 and UM-SCC1 cell lines stably transfected with JAK2 or STAT3 vectors were constructed and verified.Cell activity and cell proliferation capacity were measured to evaluate the detrimental impact of STAT3 overexpression on chemotherapy with fedratinib using Western blot,CCK8,and plate cloning assays.Results:JAK2 expression in HNSCC positively correlated with p-STAT3Y705(r=0.43,P<0.000 1)and c-Myc(r=0.48,P<0.01)expression.High p-STAT3Y705 expression positively correlated with AJCC stage(P<0.000 1)and Ki-67 expression(P<0.05).High STAT3 and p-STAT3 levels were associated with poor prognosis in patients with HNSCC.In vitro,the JAK2 inhibitor fedratinib inhibited HNSCC cell proliferation and enhanced tumor cell sensitivity to DDP and PTX.JAK2 activation promotes STAT3 phosphorylation,and STAT3 overexpression reverses the effects of fedratinib on HNSCC sensitivity to chemotherapy.Conclusions:JAK2/STAT3 signaling is elev-ated in patients with HNSCC.Targeting the JAK2/STAT3 pathway is a potential method for increasing the sensitivity of HNSCC to chemotherapy.
