Abstract
Background: Currently, the treatment for advanced hepatocellular carcinoma (HCC) is extremely limited. Ginsenoside Rg3, ganoderma lucidum polysaccharide, and Oridonin have shown great potential in anti-tumor therapy in previous studies, but low bioavailability and poor solubility seriously hinder their clinical application. Hence, new strategy for liver cancer are urgently needed. Methods: Cell viability, cell proliferation, cell migration, colony formation, tubule formation, sphere formation, and flow cytometry were used to assess the effect of a new drug, RGO-SMEDDS, (self-microemulsifying drug delivery system comprising of Rg3, ganoderma lucidum polysaccharide, and Oridonin) on HCC. Specific anti-tumor mechanisms of RGO-SMEDDS were investigated by western blot, qRT-PCR, and immunohistochemistry. Xenografts and staining with hematoxylin and eosin were used to assess the effects of RGO-SMEDDS on tumorigenesis in vivo.Results: We developed a self-microemulsifying drug delivery system (RGO-SMEDDS) for these three plant monomers. Treatment with RGO-SMEDDS resulted in induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by down-regulation of vascular endothelial growth factor and its receptor, and attenuated stemness of HCC by inhibiting EGFR/AKT/GSK-3α/β signaling pathways. In addition to excellent anti-tumor effects, RGO-SMEDDS showed considerable safety in acute toxicity tests.Conclusion: RGO-SMEDDS exerted significant anti-tumor effects by reducing angiogenesis, remodeling immune microenvironments, and promoting apoptosis, without obvious toxicities. With these attributes RGO-SMEDDS is a promising therapy for the treatment of hepatocellular carcinoma.
Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma
