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Updated: Jun 6, 2026

Assessment of Mitochondrial Health in Cancer-Associated Fibroblasts Isolated from 3D Multicellular Lung Tumor Spheroids
Published on: October 21, 2022
TRX is up-regulated by fibroblast growth factor-2 in lung carcinoma
Zheng-Hao Deng1, Hui-Qiu Cao, Yong-Bin Hu
1Department of Pathology, XiangYa School of Medicine, Central South University, Changsha, Hunan Province, China.
Abstract:
We have previously shown that exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis of the small-cell lung cancer (SCLC) cell line NCI-H446, but the underlying mechanism remains unknown. In this study, the protein profiles of FGF-2-treated and untreated NCI-H446 cells were determined by 2-D gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and bioinformatics. Differential expression analysis of the protein profiles after FGF-2 treatment identified a total of 24 protein spots, of which nine were up-regulated and 15 were down-regulated. Four proteins were identified by MALDI-TOF-MS: thioredoxin (TRX), visfatin, ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) and Cu/Zn superoxide dismutase (CuZn-SOD). Western blotting revealed that TRX was up-regulated in NCI-H446 and A549 cells treated with FGF-2. Furthermore, immunohistochemical staining confirmed that both FGF-2 and TRX were overexpressed in lung cancer tissues and could be correlated with both lymph node metastasis and clinical stage. These data indicate that TRX may be involved in the FGF-2 signaling pathway.
Insights
Fibroblast growth factor-2 (FGF-2) inhibits small-cell lung cancer (SCLC) cell death. This study identifies thioredoxin (TRX) as a key protein upregulated by FGF-2, suggesting its role in SCLC progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Exogenous fibroblast growth factor-2 (FGF-2) inhibits apoptosis in small-cell lung cancer (SCLC) cells.
- The precise molecular mechanisms underlying FGF-2's anti-apoptotic effects in SCLC are not fully understood.
Purpose of the Study:
- To elucidate the protein expression changes in NCI-H446 SCLC cells upon FGF-2 treatment.
- To identify specific proteins involved in the FGF-2 signaling pathway that may contribute to SCLC cell survival.
Main Methods:
- Proteomic analysis using 2-D gel electrophoresis and MALDI-TOF-MS to compare FGF-2-treated and untreated NCI-H446 cells.
- Bioinformatics analysis to identify differentially expressed proteins.
- Western blotting and immunohistochemical staining to validate protein expression and localization in cell lines and clinical tissues.
Main Results:
- FGF-2 treatment resulted in differential expression of 24 protein spots, with 9 up-regulated and 15 down-regulated.
- Key identified proteins included thioredoxin (TRX), visfatin, UCHL1, and CuZn-SOD.
- TRX was confirmed to be up-regulated by FGF-2 in NCI-H446 and A549 cells.
- FGF-2 and TRX were overexpressed in lung cancer tissues and correlated with lymph node metastasis and clinical stage.
Conclusions:
- Thioredoxin (TRX) is significantly up-regulated by FGF-2 in SCLC cells.
- TRX overexpression in lung cancer tissues suggests a potential role in tumor progression and links it to the FGF-2 signaling pathway.
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