Abstract

To investigate the mechanism of a Bushen-Jianpi decoction (BSJPD) in liver cancer (LC) treatment, we analyzed clinical therapy data, conducted network pharmacology analysis, and performed pharmacological experimental verification in vitro and in vivo. The univariate analysis of clinical therapy showed that the BSJPD was protective factor (p < 0.05). The network pharmacology analysis showed that 9 compounds were important nodes of BSJPD-LC therapy network. In experimental verification, the rate of apoptosis increased in the liver tumors of mice treated with the BSJPD (p < 0.05); drug serum with 20 % BSJPD inhibited cell viability (p < 0.05) and reduced the expression of PI3K, the Bcl-xL/BAD ratio, and the levels of p53 and p-Akt in HepG2 cells. Moreover, licochalcone A, alisol B, and hederagenin inhibited cell viability (p < 0.05), induced cell apoptosis (p < 0.01), reduced p-Akt levels, and increased cleaved-CASP3 (p < 0.05) and p53 expression levels in HepG2 cells. These data suggest that the BSJPD prolongs the survival of LC patients and induces apoptosis and that it may be associated with the regulation of PI3K, Akt, p53, CASP3, and Bcl-xL/BAD expression.

Highlights

  • Liver cancer (LC), a frequently occurring cancer, has become the second leading cause of cancer mortality [1,2,3]

  • Previous pharmacological studies have reported that LiuWei-Di-Huang decoction (LWDHD) and Si-Jun-Zi decoction (SJZD) are effective in treating LC, type 2 diabetes [9], inflammation, and oxidative stress [10] as well as maintaining intestinal homeostasis [11]

  • BSJPDmedicated serum, licochalcone A, alisol B, and hederagenin showed marked effects on the PI3K-Akt and apoptosisrelated pathways. These results indicated that Bushen-Jianpi decoction (BSJPD) and licochalcone A, alisol B, and hederagenin can regulate the apoptosis-related pathways in HepG2 cells

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Summary

Introduction

Liver cancer (LC), a frequently occurring cancer, has become the second leading cause of cancer mortality [1,2,3]. LC is the sixth most common cancer, and most patients are diagnosed and treated at the clinical III or IV stage [2]. Traditional Chinese medicine (TCM) plays a significant role in LC treatments. There were many studies on the treatment of LC by TCM and monomers TCM agents [7, 8]. Bushen-Jianpi decoction (BSJPD) is a combination of LiuWei-Di-Huang decoction (LWDHD) and Si-Jun-Zi decoction (SJZD). Previous pharmacological studies have reported that LWDHD and SJZD are effective in treating LC, type 2 diabetes [9], inflammation, and oxidative stress [10] as well as maintaining intestinal homeostasis [11]. As a combination of LWDHD and SJZD, BSJPD is therapeutically used in LC [12]. Because it is not easy to analyze the compounds in BSJPD by traditional pharmacological evaluations, the mechanism of action of BSJPD in LC is still unclear

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