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Multiple targeted self-emulsifying compound RGO reveals obvious anti-tumor potential in hepatocellular carcinoma
Sanxiu He1,2, Shaorong Tian2, Xiaoqian He2
1Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Abstract:
Hepatocellular carcinoma (HCC) is a highly vascularized, inflammatory, and abnormally proliferating tumor. Monotherapy is often unable to effectively and comprehensively inhibit the progress of HCC. In present study, we selected ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin as the combined therapy. These three plant monomers play important roles in anti-angiogenesis, immunological activation, and apoptosis promotion, respectively. However, the low solubility and poor bioavailability seriously hinder their clinical application. To resolve these problems, we constructed a new drug, Rg3, GLP, and oridonin self-microemulsifying drug delivery system (RGO-SMEDDS). We found that this drug effectively inhibits the progression of HCC by simultaneously targeting multiple signaling pathways. RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by downregulation of vascular endothelial growth factor and its receptor, and retarded proliferation by inhibiting the epidermal growth factor receptor EGFR/AKT/epidermal growth factor receptor/protein kinase B/glycogen synthase kinase-3 (GSK3) signaling pathway. In addition, RGO-SMEDDS showed considerable safety in acute toxicity tests. Results from this study show that RGO-SMEDDS is a promising therapy for the treatment of HCC.
Insights
This study introduces a novel drug delivery system (RGO-SMEDDS) combining three plant compounds to treat hepatocellular carcinoma (HCC). The RGO-SMEDDS effectively inhibits HCC progression by targeting multiple pathways, restoring immune function, and reducing tumor growth.
Area of Science:
- Oncology
- Pharmacology
- Drug Delivery Systems
Background:
- Hepatocellular carcinoma (HCC) is a complex malignancy characterized by high vascularization, inflammation, and proliferation.
- Monotherapy often proves insufficient for comprehensive HCC inhibition.
- Existing plant-derived compounds like ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin show promise but suffer from poor solubility and bioavailability.
Purpose of the Study:
- To develop a novel self-microemulsifying drug delivery system (RGO-SMEDDS) for combined ginsenoside Rg3, GLP, and oridonin.
- To evaluate the efficacy of RGO-SMEDDS in inhibiting HCC progression through multi-targeted mechanisms.
- To assess the safety profile of the RGO-SMEDDS formulation.
Main Methods:
- Formulation of a self-microemulsifying drug delivery system (SMEDDS) encapsulating ginsenoside Rg3, GLP, and oridonin (RGO-SMEDDS).
- Evaluation of RGO-SMEDDS's effects on immune function, angiogenesis, and tumor cell proliferation.
- Investigation of RGO-SMEDDS's impact on key signaling pathways including EGFR/AKT/GSK3.
- Acute toxicity testing of the RGO-SMEDDS formulation.
Main Results:
- RGO-SMEDDS effectively inhibits HCC progression by simultaneously targeting multiple signaling pathways.
- The formulation restored immune function by suppressing immunosuppressive cytokines and M2-polarized macrophages.
- RGO-SMEDDS reduced angiogenesis via downregulation of vascular endothelial growth factor (VEGF) and its receptor.
- Tumor cell proliferation was retarded by inhibiting the EGFR/AKT/GSK3 signaling pathway.
- RGO-SMEDDS demonstrated considerable safety in acute toxicity tests.
Conclusions:
- RGO-SMEDDS represents a promising multi-targeted therapeutic strategy for hepatocellular carcinoma.
- The novel drug delivery system overcomes the limitations of poor solubility and bioavailability of individual compounds.
- This approach offers a potentially effective and safe treatment option for HCC.
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