Regulatory mechanism of the Glabrene against non-small cell lung cancer by suppressing FGFR3

作者全名："He, Miao; Wu, Huiling; Hu, Lingjing; Liu, Nan; Zhang, Guoduo; Wang, Shumei"

作者地址："[He, Miao; Wu, Huiling; Wang, Shumei] Chongqing Med Univ, Coll Tradit Chinese Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [He, Miao; Hu, Lingjing; Liu, Nan; Zhang, Guoduo] Hosp Tradit Chinese Med, Dept Hematol & Oncol, Chongqing Oncol Hematol Dept, Chongqing 400011, Peoples R China; [Wu, Huiling] Chongqing Med Univ, Bone & joint Rehabil Dept, Affiliated Rehabil Hosp, Chongqing, Peoples R China"

通信作者："Wang, SM (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Zhang, GD (通讯作者)，Hosp Tradit Chinese Med, Dept Hematol & Oncol, Chongqing Oncol Hematol Dept, Chongqing 400011, Peoples R China."

来源：ENVIRONMENTAL TOXICOLOGY

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001189097400001

JCR分区：Q1

影响因子：4.4

年份：2024

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：EMT; ERK1/2; FGFR3; Glabrene; NSCLC

摘要："Background Non-small cell lung cancer (NSCLC) is a highly malignant tumor with limited effective treatment options. This study aimed to investigate the regulatory mechanism of Glabrene on NSCLC through its interaction with FGFR3. Methods HCC827 cells were implanted into nude mice and treated with Glabrene. Tumor volume was monitored at 0, 3, 6, and 9 days after medical treatment. Tissue analysis included Hematoxylin and Eosin (HE) and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP Nick End Labeling (TUNEL) staining, as well as immunohistochemistry for Ki67, ERK1/2, and p-ERK1/2 expression. Cell viability was determined with the CCK8 method. We utilized immunofluorescence techniques to observe apoptosis, as well as the levels of E-cadherin and Vimentin expression. Cellular proliferation was determined via plate cloning assay and cellular mobility was determined via scratch assay. Cellular invasion ability was assessed via a transwell assay. mRNA and protein levels of FGFR3, MMP1, MMP9, vimentin, E-cadherin, ERK1/2, and p-ERK1/2 were detected via qPCR and Western blot. IGF-1, VEGF, and Estradiol (E2) levels were measured through Enzyme linked immunosorbent assay (ELISA). Results This study verified that Glabrene was capable of suppressing tumor growth in NSCLC mice, reversing tumor tissue's pathological morphology, attenuating the capacities of cancerous cells' proliferation, migration, and invasion, and leading to apoptosis. Besides, Glabrene could reduce the FGFR3 expression in HCC827 cells. Over-expression of FGFR3 promotes the proliferation of HCC827 cells, increase both contents of IGF-1, VEGF, and E2, and expressions of MMP1, MMP9, vimentin, and p-ERK1/2, while Glabrene inhibited FGFR3. Glabrene, and inhibition of FGFR3 expression were capable of decreasing FGFR3, MMP1, MMP9, vimentin, and p-ERK1/2 expression, as well as contents of IGF-1, VEGF, and E2 in model mice and HCC827 cells, and promoting the expression of E-cadherin. Conclusion Glabrene has the potential as a therapeutic agent for NSCLC by reducing cancer invasion and migration through the inhibition of ERK1/2 phosphorylation and suppression of epithelial-mesenchymal transition (EMT)."

基金机构：Construction Project of Famous Old Chinese Medicine Expert Inheritance Studio of Chongqing Hospital of Traditional Chinese Medicine; Program for Xinglin Scholars Scientifc Research Promotion Plan of Chengdu University of Traditional Chinese Medicine [YYZX2022141]; Fifth batch of national TCM clinical outstanding Talents Program; National Traditional Chinese Medicine Innovation Backbone Talent Project; [cqzyymzygzs-003]

基金资助正文：the Construction Project of Famous Old Chinese Medicine Expert Inheritance Studio of Chongqing Hospital of Traditional Chinese Medicine (Grant Number: cqzyymzygzs-003); the Program for Xinglin Scholars Scientifc Research Promotion Plan of Chengdu University of Traditional Chinese Medicine (Grant Number: YYZX2022141); the fifth batch of national TCM clinical outstanding Talents Program; National Traditional Chinese Medicine Innovation Backbone Talent Project