Shenqi Fuzheng Injection (SFI) Enhances IFN-α Inhibitory Effect on Hepatocellular Carcinoma Cells by Reducing VEGF Expression: Validation by Gene Silencing Technique.

Xiaoheng Chen,Zhiguo Ding,Hui Long Li,Tangshun Wang,Jinxiang Fu,Xiaoguang Shi,Xin Wang,Rui Hu,Lu Li,Tao Zhang,Sheng Huang,Shuo Qi,Junhui Wang,Xiang Gao,Feng Xue,Lei Zhang,Xinai Li,Zhe Li,Bei He

doi:10.1155/2019/8084109

Abstract

Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.

Highlights

Hepatocellular carcinoma (HCC) is a primary liver tumor and the most difficult human malignancy to treat. [1]
High rates of recurrence and metastasis after operation have become a bottleneck for improving the long-term efficacy, which is a key point in overcoming HCC
In the analysis of the inhibition ratio of MHCC97L cells with a low dose of IFN-α (6000 IU), Shenqi Fuzheng Injection (SFI) (0.5 g/L), and IFN-α (6000 IU) + SFI (0.5 g/L), the results showed that the inhibition ratio of a low dose of IFN-α (6000 IU) was 29.5%, while the value for SFI (0.5 g/L) was -27.4%, and IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α (6000 IU) and the SFI (0.5 g/L) group (P < 0.01, compared to IFN-α and the SFI control group) (Figure 1)

Summary

Introduction

Hepatocellular carcinoma (HCC) is a primary liver tumor and the most difficult human malignancy to treat. [1]. Hepatocellular carcinoma (HCC) is a primary liver tumor and the most difficult human malignancy to treat. High rates of recurrence and metastasis after operation have become a bottleneck for improving the long-term efficacy, which is a key point in overcoming HCC. Interferon (IFN-) α is a chemotherapeutic drug that is widely used in the clinical treatment of HCC [2] and has various effects, such as resistance to viral infections, immune function, inhibition of cell proliferation, and apoptosis induction [3,4,5,6]. Vascular endothelial growth factor (VEGF) is a well-characterized angiogenic factor known to stimulate angiogenesis within a tumor [7]. Studies have shown that increased expression of VEGF is an important factor in the recurrence and metastasis of HCC [8]

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Discussion

Conclusion