Targeting CDH11 with celecoxib and derivatives to suppress esophageal squamous cell carcinoma proliferation and invasion

IF 2.9 4区医学 Q2 PATHOLOGY

Pathology, research and practice Pub Date : 2025-05-27 DOI:10.1016/j.prp.2025.156042

Lin Xiao , Bingbing Yang , Yijuan Zhou , Jiarui Zhang , Xiaoyan Zhang , Wanjing Yang , Minjing Sun , Mengmeng Li , Xueyan Zhao , Fang Tian

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Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with limited therapeutic options. Cadherin-11 (CDH11) has been implicated in tumor progression, but its role in ESCC remains unclear.

Methods

CDH11 expression was analyzed in ESCC tissues and cell lines. Functional assays (proliferation, migration, invasion) and xenograft models were employed to assess CDH11’s role. Celecoxib and its derivative 2,5-dimethyl celecoxib (DMC) were evaluated as CDH11-targeted inhibitors.

Results

CDH11 was overexpressed in ESCC tissues and correlated with lymph node metastasis and poor prognosis. Knockdown of CDH11 suppressed ESCC proliferation and invasion (P < 0.05), while overexpression exacerbated these phenotypes. Celecoxib and DMC directly bound CDH11 and inhibited ESCC growth in vitro and in vivo (IC₅₀: 21.61–43.34 μM). Mechanistically, CDH11 knockdown attenuated JAK-STAT3 and AKT signaling.

Conclusion

CDH11 is a novel therapeutic target in ESCC, and its inhibition by celecoxib/DMC offers a promising strategy for ESCC treatment.

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塞来昔布及其衍生物靶向CDH11抑制食管鳞状细胞癌的增殖和侵袭

食管鳞状细胞癌（ESCC）是一种高度侵袭性的恶性肿瘤，治疗选择有限。Cadherin-11 （CDH11）与肿瘤进展有关，但其在ESCC中的作用尚不清楚。方法分析scdh11在ESCC组织和细胞系中的表达。采用功能分析（增殖、迁移、侵袭）和异种移植模型来评估CDH11的作用。塞来昔布及其衍生物2,5-二甲基塞来昔布（DMC）被评价为cdh11靶向抑制剂。结果scdh11在ESCC组织中过表达，与淋巴结转移和不良预后相关。低表达CDH11抑制ESCC的增殖和侵袭（P <； 0.05），而过表达则加重了这些表型。塞来昔布和DMC直接结合CDH11，抑制体外和体内ESCC生长（IC50: 21.61 ~ 43.34 μM）。机制上，CDH11敲低可减弱JAK-STAT3和AKT信号。结论cdh11是ESCC的一个新的治疗靶点，塞来昔布/DMC抑制cdh11为ESCC的治疗提供了一个有前景的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pathology, research and practice 医学-病理学

CiteScore

5.00

自引率

3.60%

发文量

405

审稿时长

24 days

期刊介绍： Pathology, Research and Practice provides accessible coverage of the most recent developments across the entire field of pathology: Reviews focus on recent progress in pathology, while Comments look at interesting current problems and at hypotheses for future developments in pathology. Original Papers present novel findings on all aspects of general, anatomic and molecular pathology. Rapid Communications inform readers on preliminary findings that may be relevant for further studies and need to be communicated quickly. Teaching Cases look at new aspects or special diagnostic problems of diseases and at case reports relevant for the pathologist''s practice.