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Exploring the Therapeutic Potential of Oridonin in the Treatment of Laryngeal Cancer: A Comprehensive Strategy
Rui Zhang1, Lei Ren2, Jiabin Hou1
1Department of Otolaryngology Head and Neck Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Abstract:
Laryngeal cancer (LC) is one of the most common malignant tumors of the head and neck, with high morbidity and mortality rates worldwide. Oridonin (Ori), a natural tetracyclic diterpenoid, exhibits notable anti-tumor properties. However, its efficacy and underlying mechanism in LC remain to be elucidated. This study employed comprehensive network pharmacology, molecular docking, and molecular dynamic simulation to investigate the molecular targets and mechanisms underlying the anti-LC effects of Ori, followed by in vitro validation of its key mechanisms. A total of 172 potential therapeutic targets of Ori for LC were identified. GO and KEGG analyses indicated that Ori's anti-LC mechanism primarily involved the PI3K-Akt, Ras, MAPK, and Rap1 signaling pathways. The PPI network and molecular docking analyses revealed that AKT1, EGFR, and MAPK1 are potential core targets of Ori. Additionally, molecular dynamics simulations and bioinformatics analyses further confirmed that these proteins are key candidate targets. In vitro, Ori inhibited the proliferation of LC Hep-2 and TU212 cells, induced apoptosis, arrested the cell cycle at the G1 phase, and suppressed migration and invasion. WB assays further showed that Ori significantly downregulated p-AKT expression in the PI3K/AKT pathway. These findings indicate that Ori represents a promising therapeutic candidate for LC.
Insights
Oridonin (Ori) shows promise in treating laryngeal cancer (LC) by inhibiting cell growth and inducing apoptosis. Its anti-cancer effects are linked to the PI3K-Akt signaling pathway, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Laryngeal cancer (LC) presents significant global health challenges due to high morbidity and mortality.
- Oridonin (Ori), a natural compound, possesses known anti-tumor activities, but its specific role in LC requires detailed investigation.
Purpose of the Study:
- To elucidate the molecular targets and mechanisms of Oridonin (Ori) in laryngeal cancer (LC).
- To validate the in vitro efficacy and key pathways affected by Ori in LC.
Main Methods:
- Network pharmacology, molecular docking, and molecular dynamics simulations were used to identify Ori's targets and pathways in LC.
- In vitro assays, including cell proliferation, apoptosis, cell cycle, migration, invasion, and Western blot (WB), were performed for validation.
Main Results:
- 172 potential therapeutic targets for Ori in LC were identified.
- Key signaling pathways involved include PI3K-Akt, Ras, MAPK, and Rap1. AKT1, EGFR, and MAPK1 were identified as core targets.
- Ori inhibited LC cell proliferation, induced apoptosis, arrested the cell cycle at G1, and reduced migration/invasion. Downregulation of p-AKT was observed.
Conclusions:
- Oridonin (Ori) demonstrates significant anti-cancer effects against laryngeal cancer cells in vitro.
- The PI3K-Akt pathway, specifically the downregulation of p-AKT, is a crucial mechanism underlying Ori's efficacy in LC.
- Ori is a promising therapeutic candidate for laryngeal cancer treatment.
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