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[Inhibition of eIF families expression and angiogenesis for human laryngeal carcinoma by elemene administration]
Lei Tao1, Liang Zhou, Lu-ying Zheng
1Department of Otorhinolaryngology, Eye Ear Nose & Throat Hospital of Fudan University, Shanghai 200031, China.
Objective:
To investigate the inhibitory effect of elemene on laryngeal carcinoma (Hep-2 cells) xenograft growth in nude mice and its mechanisms, and to explore the relationship between the expression of eukaryotic initiation factor families (eIF4E & eIF4G) and angiogenesis factors (bFGF & VEGF) after the administration of elemene.
Methods:
Human laryngeal carcinoma cells from Hep-2 cell strain were transplanted subcutaneously to BALB/c-nu/nu nude mice to produce tumors (42 nude mice were separated into seven groups to be treated by intraperitoneal injection). The tumor volume, tumor weight and tumor inhibition rate were evaluated, the expression of eIF4E, eIF4G, bFGF, VEGF and microvessel density were estimated by paraffin-embedded sections of seven groups' tumor samples analyzed utilizing immunohistochemical streptavidin peroxidase technique.
Results:
Elemene could inhibit the tumor growth in vivo. A significant suppression of tumor growth was observed when the dosage was increased. The tumor inhibition rates (IR) of elemene 50 mg/kg, 100 mg/kg and 200 mg/kg treated group were 5.2% , 41.7% and 50. 5% respectively. The IR of 100 mg/kg elemene (41.7%) was not significantly different with that of 3 mg/kg cisplatin (44.6%), and the IR of the drug combination (100 mg/kg elemene + 3 mg/kg cisplatin) was 51.2%. Compared with control groups the protein expression of eIF4E, eIF4G, bFGF and VEGF were significantly inhibited by elemene (P < 0.05), and the microvessel density in elemene treated groups decreased (P < 0.05). The tumor inhibition rate of combined elemene 100 mg/kg and cisplatin 3 mg/kg was 51.2%.
Conclusions:
Elemene could inhibit the subcutaneous plantation of human laryngeal carcinoma in nude mice and its mechanism may be associated with inhibited expression of eIF families and angiogenesis factors. The combination of elemene and cisplatin could promote the synergistic effect on chemotherapy in the target tumor cells.
Insights
Elemene effectively inhibits laryngeal carcinoma growth in mice by reducing key protein expression involved in cell growth and blood vessel formation. Combining elemene with cisplatin enhances this anti-cancer effect, suggesting a synergistic therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Context:
- Laryngeal carcinoma poses a significant health challenge, necessitating novel therapeutic strategies.
- Elemene, a natural compound, has shown potential anti-cancer properties.
- Understanding the molecular mechanisms underlying elemene's efficacy is crucial for its clinical application.
Purpose:
- To evaluate the in vivo inhibitory effect of elemene on laryngeal carcinoma xenografts.
- To investigate the impact of elemene on the expression of eukaryotic initiation factor families (eIF4E, eIF4G) and angiogenesis factors (bFGF, VEGF).
- To explore the potential synergistic effect of combining elemene with cisplatin.
Summary:
- Elemene demonstrated dose-dependent inhibition of laryngeal carcinoma xenograft growth in nude mice.
- Treatment with elemene significantly reduced the expression of eIF4E, eIF4G, bFGF, and VEGF, and decreased microvessel density.
- The combination of elemene and cisplatin exhibited a synergistic effect, enhancing tumor growth inhibition.
Impact:
- Elemene exhibits anti-tumor activity against laryngeal carcinoma, potentially through the downregulation of key proteins involved in translation initiation and angiogenesis.
- The findings suggest that elemene, alone or in combination with cisplatin, could be a promising therapeutic agent for laryngeal cancer.
- This study provides a mechanistic basis for the clinical investigation of elemene in laryngeal cancer treatment.
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