Related Experiment Video
Updated: May 1, 2026
High-Efficiency Transduction of Liver Cancer Cells by Recombinant Adeno-Associated Virus Serotype 3 Vectors
Published on: March 22, 2011
Signal transducer and activator of transcription 3 as molecular therapy for non-small-cell lung cancer
Cheng-Yi Wang1, Ting-Ting Chao, Wei-Tien Tai
1*Medical Research Center, †Department of Internal Medicine, Cardinal Tien Hospital, Fu Jen Catholic University, New Taipei City, Taiwan; ‡Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; §Department of Medical Research, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan; ‖National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan; ¶Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; #Department of Pathology, Cardinal Tien Hospital, Fu Jen Catholic University, New Taipei City, Taiwan; **Department of Emergency Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan; ††Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan; and ‡‡Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University, Taipei, Taiwan.
Introduction:
Targeting signal transducer and activator of transcription 3 (STAT3), a transcription factor that modulates survival-directed transcription, is often persistently activated in epidermal growth factor receptor (EGFR) wild-type non-small-cell lung cancer (NSCLC). The aim of this study was to determine whether sorafenib and its derivative can inhibit EGFR wild-type NSCLC via STAT3 inactivation.
Methods:
EGFR wild-type NSCLC cell lines (A549 H292 H322 H358 and H460) were treated with sorafenib or SC-1, a sorafenib derivative that closely resembled sorafenib structurally but was devoid of kinase inhibitory activity. Apoptosis and signal transduction were analyzed. In vivo efficacy was determined in nude mice with H460 and A549 xenograft.
Results:
SC-1 had better effects than sorafenib on growth inhibition and apoptosis in all tested EGFR wild-type NSCLC lines. SC-1 reduced STAT3 phosphorylation at tyrosine 705 in all tested EGFR wild-type NSCLC cells. The expression of STAT3-driven genes, including cylcin D1 and survivin, was also repressed by SC-1. Ectopic expression of STAT3 in H460 cells abolished apoptosis in SC-1-treated cells. Sorafenib and SC-1 enhanced Src homology-2 containing protein tyrosine phosphatase-1 (SHP-1) activity, whereas knockdown of SHP-1, but not SHP-2 or protein-tyrosine phosphatase 1B (PTP-1B), by small interference RNA reduced SC-1-induced apoptosis. SC-1 significantly reduced H460 and A549 tumor growth in vivo through SHP-1/STAT3 pathway.
Conclusions:
SC-1 provides proof that targeting STAT3 signaling pathway may be a novel approach for the treatment of EGFR wild-type NSCLC.
Insights
A novel sorafenib derivative, SC-1, effectively inhibits epidermal growth factor receptor (EGFR) wild-type non-small-cell lung cancer (NSCLC) by inactivating the signal transducer and activator of transcription 3 (STAT3) pathway.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is crucial for survival signaling and is often hyperactivated in EGFR wild-type non-small-cell lung cancer (NSCLC).
- Targeting STAT3 presents a potential therapeutic strategy for NSCLC lacking EGFR mutations.
Purpose of the Study:
- To investigate the efficacy of sorafenib and its derivative SC-1 in inhibiting EGFR wild-type NSCLC.
- To determine if STAT3 inactivation mediates the anti-cancer effects of SC-1.
Main Methods:
- EGFR wild-type NSCLC cell lines were treated with sorafenib or SC-1.
- Apoptosis, signal transduction, and STAT3 phosphorylation were analyzed.
- In vivo efficacy was assessed using xenograft models in nude mice.
Main Results:
- SC-1 demonstrated superior growth inhibition and apoptosis induction compared to sorafenib in all tested NSCLC cell lines.
- SC-1 significantly reduced STAT3 phosphorylation and the expression of STAT3-driven genes.
- SC-1 enhanced Src homology-2 containing protein tyrosine phosphatase-1 (SHP-1) activity, and SHP-1 knockdown abrogated SC-1-induced apoptosis.
- SC-1 effectively suppressed tumor growth in vivo via the SHP-1/STAT3 pathway.
Conclusions:
- SC-1 effectively targets the STAT3 signaling pathway in EGFR wild-type NSCLC.
- Targeting the STAT3 pathway with agents like SC-1 represents a promising novel therapeutic approach for NSCLC.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:39lncRNA - Long Non-coding RNAs