HIF-1α RNAi Combined with Asparagus Polysaccharide Exerts an Antiangiogenesis Effect on Hepatocellular Carcinoma In Vitro and In Vivo.

Tingting Zhu,Dongwei Xing,Minguang Zhang,Ziwei Cheng,Xiaolin Peng

doi:10.1155/2021/9987383

Abstract

Background Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and life-threatening malignancies globally. Hypoxia activates hypoxia-inducible factor-1α (HIF-1α), which is the key factor in promoting angiogenesis in HCC. Currently, there are few studies on the effects of HIF-1α-targeted gene therapy combined with traditional Chinese herbal extracts. Objective We investigated the effects of HIF-1α RNA interference (RNAi) combined with asparagus polysaccharide (ASP) on HCC in vitro and in vivo. Methods CCK-8, wound-healing, transwell, and human umbilical vein endothelial cell tube formation assays were performed to evaluate the proliferation, migration, invasion, and angiogenesis of HCC cells in vitro. In addition, western blotting, qPCR, and immunohistochemistry were performed to detect the expression of HIF-1α, vascular endothelial growth factor, AKT, p-AKT, ERK, p-ERK, and CD34 in HCC cells. Results The combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep1 and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. In addition, this combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways. These results were observed both in vitro and in vivo. Conclusion Our study indicates that HIF-1α RNAi combined with ASP inhibits angiogenesis in HCC via the PI3K and MAPK signaling pathways. Thus, we suggest that this combination may be an effective method for the comprehensive treatment of HCC, which may provide new ideas for the treatment of other malignant tumors.

Highlights

Hepatocellular carcinoma (HCC) is a common malignancy of the digestive system
To assess the inhibitory effect of asparagus polysaccharide (ASP) combined with Hypoxiainducible factor-1α (HIF-1α) RNA interference (RNAi) on migration and invasion, we treated HCC cells (SK-Hep1 and Hep-3B) with HIF-1α RNAi for 24 h or 48 h together with ASP at 10 mg/mL. e results showed that compared with the control group, the migration ability of cells was decreased after treatment with ASP or HIF-1α RNAi alone, and the effect was similar in both groups, indicating that ASP or HIF-1α RNAi could affect the migration ability of HCC cells
The migration ability of cells in the group treated with HIF-1α RNAi combined with ASP was further inhibited compared with that of cells treated with ASP or HIF-1α RNAi alone (Figures 1(a), 1(b), 2(a), and 2(b))

Summary

Introduction

Hepatocellular carcinoma (HCC) is a common malignancy of the digestive system. Globally, the number of new cases reaches 841,000 every year, making it the sixth most prevalent malignant tumor, and the number of deaths is 782,000 per year, ranking second among malignant tumors. It has been well demonstrated that HIF-1α extensively regulates hypoxia gene expression and aggressive phenotypes of cancer cells, leading to metabolic changes, increased survival, invasion, migration, angiogenesis, and other related signal transduction [6, 7]. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and is one of the most prevalent and lifethreatening malignancies globally. E combination of HIF-1α RNAi and ASP significantly inhibited the proliferation, migration, invasion, and angiogenesis of SK-Hep and Hep-3B cells compared with the use of HIF-1α RNAi or ASP alone. This combined treatment was shown to exert these effects by regulating the PI3K and MAPK signaling pathways

Methods

Results

Conclusion