Multiple targeted self-emulsifying compound RGO reveals obvious anti-tumor potential in hepatocellular carcinoma

Sanxiu He; Shaorong Tian; Xiaoqian He; Xin Le; Yijiao Ning; Jialin Chen; Hongyi Chen; Junhao Mu; Ke Xu; Qin Xiang; Yue Wu; Jiong Chen; Tingxiu Xiang

doi:10.1016/j.omto.2021.08.008

Multiple targeted self-emulsifying compound RGO reveals obvious anti-tumor potential in hepatocellular carcinoma

Mol Ther Oncolytics. 2021 Aug 19:22:604-616. doi: 10.1016/j.omto.2021.08.008. eCollection 2021 Sep 24.

Authors

Sanxiu He^{1

2}, Shaorong Tian², Xiaoqian He², Xin Le², Yijiao Ning², Jialin Chen³, Hongyi Chen⁴, Junhao Mu², Ke Xu², Qin Xiang², Yue Wu², Jiong Chen⁵, Tingxiu Xiang²

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
³ Chongqing Traditional Chinese Medicine Hospital, Chongqing, China.
⁴ Chongqing College of Humanities, Science & Technology, Chongqing, China.
⁵ College of Pharmacy, 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.

Keywords: epidermal growth factor receptor; ganoderma lucidum polysaccharide; ginsenoside Rg3; hepatocellular carcinoma; oridonin.