Related Experiment Video
Updated: Dec 13, 2025
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
TGF-β downregulation overcomes gemcitabine resistance in oral squamous cell carcinoma
Yun-Ze Xuan1,1, Cheng-Ri Jin1,1, Kang-Juan Yang2
1Department of Dentistry, Affiliated Hospital of Yanbian University, Yanji, Jilin, China.
Objective:
The aim of this study was to explore the mechanisms by which oral cancer acquires resistance to gemcitabine.
Methods:
Oral squamous cell carcinoma (OSCC) cells were treated with gemcitabine upon infection or with a lentivirus harboring short hairpin RNA (shRNA) targeted to transforming growth factor-β (TGF-β). Then, Western blot, ELISA, migration assay, MTT assay, and animal experiments were used to explore the mechanism of resistance to gemcitabine treatment.
Results:
After the treatment of non-transfected cells with gemcitabine, NF-κB and AKT activities were increased, which may have induced the OSCC resistance to gemcitabine. Then, we found that TGF-β downregulation effectively reduced NF-κB and AKT phosphorylation levels after the administration of gemcitabine and increased the OSCC sensitivity to gemcitabine, resulting in cell death and the blunting of OSCC resistance to gemcitabine. The EMT was also reduced by TGF-β downregulation combined with gemcitabine treatment.
Conclusion:
Cellular levels of TGF-β constitute an important factor in gemcitabine resistance and TGF-β silencing might represent a novel and potent strategy for overcoming OSCC resistance to gemcitabine.
Insights
Transforming growth factor-beta (TGF-β) drives oral cancer resistance to gemcitabine by activating NF-κB and AKT. Silencing TGF-β enhances gemcitabine efficacy, offering a potential strategy to overcome treatment resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oral squamous cell carcinoma (OSCC) poses a significant health challenge.
- Gemcitabine is a chemotherapeutic agent used in cancer treatment.
- Understanding mechanisms of drug resistance is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the molecular mechanisms underlying gemcitabine resistance in OSCC.
- To identify potential therapeutic targets for overcoming this resistance.
Main Methods:
- OSCC cells were treated with gemcitabine and/or TGF-β targeting shRNA.
- Assays included Western blot, ELISA, migration, and MTT assays.
- In vivo animal experiments were conducted to validate findings.
Main Results:
- Gemcitabine treatment increased NF-κB and AKT activity in OSCC cells, correlating with resistance.
- Downregulation of TGF-β significantly reduced NF-κB and AKT phosphorylation.
- TGF-β silencing enhanced gemcitabine sensitivity, induced cell death, and reduced epithelial-mesenchymal transition (EMT).
Conclusions:
- Cellular TGF-β levels are a key determinant of gemcitabine resistance in OSCC.
- TGF-β silencing presents a promising strategy to sensitize OSCC to gemcitabine and overcome resistance.
- Targeting TGF-β may improve chemotherapeutic efficacy in oral cancer treatment.
More Related Videos
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
09:56Patient-derived Heterogeneous Xenograft Model of Pancreatic Cancer Using Zebrafish Larvae as Hosts for Comparative Drug Assessment
Published on: April 30, 2019
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
01:20The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...