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Updated: Jun 19, 2026

Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Dendrobine inhibits anaplastic thyroid cancer progression by targeting the JAK-STAT3 pathway
1Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.
Objective:
This study aimed to investigate the antitumor effects of dendrobine on ATC cells and its mechanism targeting the JAK-STAT3 pathway.
Methods:
Human ATC cell lines (CAL-62 and 8505C) were treated with dendrobine (DEM). Detect cell viability, cell proliferation, cell apoptosis, cell migration and invasion. The expressions of E-cad, N-cad and Vim were detected by IF. JAK1, JAK2, STAT3 and their phosphorylated forms were quantified by WB. To probe pathway reversibility, cells were pretreated with IL-6 (20 ng/mL) or STAT3-siRNA before dendrobine exposure. In vivo, 6-week-old male BALB/c nude mice with 8505C xenografts were administered dendrobine (10 or 40 mg/kg/d) or saline for 21 d.
Results:
Dendrobine reduced the viability of CAL-62 and 8505C cells, with 5 μM dendrobine achieving the most pronounced inhibition (P < 0.001). Dendrobine treatment markedly suppressed cell proliferation (P < 0.05) and colony formation (P < 0.001), while increasing apoptosis (P < 0.01). Dendrobine also inhibited migration and invasion (P < 0.05), upregulated E-cad expression (P < 0.001), downregulated N-cad and Vim expression (P < 0.05), suggesting EMT inhibition. WB analysis confirmed that dendrobine suppressed phosphorylation of JAK1, JAK2, and STAT3 (P < 0.05). However, IL-6 pretreatment reversed these effects by restoring p-JAK1, p-JAK2, and p-STAT3 levels (P < 0.001) and partially rescuing cell proliferation and migration (P < 0.001). Conversely, STAT3-siRNA transfection enhanced dendrobine's inhibitory effects on proliferation, invasion, and migration (P < 0.05) and further reduced JAK-STAT3 phosphorylation (P < 0.05). In vivo, Dendrobine reduced tumor volume and weight (P < 0.001), decreased IL-6 content in tumors (P < 0.05), improved liver function indices by reducing AST, ALT and ALP activities (P < 0.05), and exhibited no nephrotoxic effects.
Conclusion:
Dendrobine exerts antitumor effects in ATC by targeting the JAK-STAT3 pathway, providing a promising therapeutic candidate.
Insights
Dendrobine shows significant antitumor effects against anaplastic thyroid carcinoma (ATC) by inhibiting the JAK-STAT3 pathway. This natural compound suppressed cell growth and metastasis in vitro and in vivo.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Anaplastic thyroid carcinoma (ATC) is an aggressive malignancy with limited treatment options.
- The Janus kinase-STAT3 (JAK-STAT3) signaling pathway is frequently dysregulated in various cancers, including ATC, promoting tumor growth and survival.
Purpose of the Study:
- To investigate the potential antitumor effects of dendrobine on ATC cells.
- To elucidate the underlying mechanism of dendrobine's action, specifically its targeting of the JAK-STAT3 pathway.
Main Methods:
- Human ATC cell lines (CAL-62, 8505C) were treated with dendrobine. Assays included cell viability, proliferation, apoptosis, migration, and invasion.
- Protein expression (E-cad, N-cad, Vim, JAK1, JAK2, STAT3, and their phosphorylated forms) was analyzed via Western blot and immunofluorescence.
- Pathway reversibility was assessed using IL-6 or STAT3-siRNA pretreatment.
- An in vivo xenograft mouse model was used to evaluate dendrobine's efficacy and safety.
Main Results:
- Dendrobine significantly inhibited ATC cell viability, proliferation, migration, and invasion while inducing apoptosis.
- Dendrobine upregulated E-cadherin and downregulated N-cadherin and Vimentin, indicating inhibition of epithelial-mesenchymal transition (EMT).
- Dendrobine suppressed the phosphorylation of JAK1, JAK2, and STAT3, key components of the JAK-STAT3 pathway. IL-6 pretreatment reversed these effects, while STAT3-siRNA enhanced dendrobine's efficacy.
- In vivo studies showed dendrobine reduced tumor volume and weight, improved liver function indices, and exhibited no nephrotoxicity.
Conclusions:
- Dendrobine demonstrates potent antitumor activity against ATC.
- The mechanism involves the inhibition of the JAK-STAT3 signaling pathway.
- Dendrobine represents a promising therapeutic candidate for ATC treatment.
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