白花丹醌靶向GLUT1/MMP-2轴以抑制口腔鳞状细胞癌进展。

Plumbagin targets the GLUT1/MMP-2 axis to inhibit oral squamous cell carcinoma progression.

作者信息

He Fei, Wang Weiqi, Elayah Sadam Ahmed, Xie Linyang, Yu Ming, Gong Yuxin, Cui Hao, Liang Xiang, Tu Junbo, Han Ying, Na Sijia

机构信息

Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, 98 West 5th Road, Xi'an, Shaanxi, 710004, China.

Department of Oral and Maxillofacial Surgery, College of Stomatology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, China.

出版信息

Cancer Cell Int. 2025 Jul 28;25(1):283. doi: 10.1186/s12935-025-03915-7.

DOI:10.1186/s12935-025-03915-7

PMID:40722096

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12302832/

Abstract

AIM

This study aimed to investigate the clinicopathological characteristics and prognostic value of GLUT1 in oral squamous cell carcinoma (OSCC) and the effect of plumbagin (PLB) on inhibiting OSCC invasion and metastasis through the GLUT1/Matrix Metalloproteinase 2 (MMP2) axis pathway.

MATERIALS AND METHODS

One hundred and twenty human OSCC specimens were collected. Immunohistochemistry was performed to analyze the expression, clinicopathological characteristics, and prognostic value of GLUT1 in these specimens. Cal27 and SCC9 cell lines were used to investigate the role of PLB in cell proliferation, migration, invasion, and metastasis in vitro and in vivo.

RESULTS

Immunohistochemistry showed significant associations between GLUT1 expression and MMP2, tumor recurrence, lymphatic metastasis, and TNM stage. In vitro and in vivo experiments demonstrated that PLB inhibited OSCC cell proliferation, migration, and invasion by downregulating GLUT1 and MMP2. WZB117, a GLUT1 inhibitor, also reduced cell colony formation, migration, and invasion. However, univariate and multivariate analyses indicated that GLUT1 expression was not an independent prognostic marker for OSCC overall and disease-free survival.

CONCLUSIONS

The findings demonstrated a novel anti-cancer mechanism of plumbagin, inhibiting OSCC invasion and migration by suppressing the GLUT1/MMP2 axis pathway, providing a theoretical basis for the future clinical use of plumbagin in the treatment of OSCC.

摘要

目的

本研究旨在探讨葡萄糖转运蛋白1（GLUT1）在口腔鳞状细胞癌（OSCC）中的临床病理特征及预后价值，以及白花丹素（PLB）通过GLUT1/基质金属蛋白酶2（MMP2）轴途径抑制OSCC侵袭和转移的作用。

材料与方法

收集120例人OSCC标本。采用免疫组织化学法分析这些标本中GLUT1的表达、临床病理特征及预后价值。利用Cal27和SCC9细胞系研究PLB在体外和体内对细胞增殖、迁移、侵袭和转移的作用。

结果

免疫组织化学显示GLUT1表达与MMP2、肿瘤复发、淋巴结转移及TNM分期之间存在显著相关性。体外和体内实验表明，PLB通过下调GLUT1和MMP2抑制OSCC细胞增殖、迁移和侵袭。GLUT1抑制剂WZB117也减少了细胞集落形成、迁移和侵袭。然而，单因素和多因素分析表明，GLUT1表达并非OSCC总体生存和无病生存的独立预后标志物。