Anticancer Action of Xiaoxianxiong Tang in Non-Small Cell Lung Cancer by Pharmacological Analysis and Experimental Validation

Rongzhen Ding,Shuliu Sang,Lijing Jiao,Yinan Yin,Yabin Gong,Ling Xu,Yichao Wang,Ling Bi,Ho Lin

doi:10.1155/2021/9930082

Abstract

Xiaoxianxiong Tang (XXXT) is a well-known traditional Chinese medicine formula. Evidence is emerging supporting the benefits of XXXT in ameliorating therapy for non-small cell lung cancer (NSCLC). The purpose of this study aimed to explore the effects and mechanisms of XXXT through network pharmacological analysis and biological validation. TCMSP database was used to identify potentially active compounds in XXXT with absorption, distribution, metabolism, excretion screening, and their potential targets. The disease targets related to NSCLC were predicted by searching for Therapeutic Target database, GeneCards database, DrugBank database, and DisGeNET database. Of the 4385 NSCLC-related targets, 156 targets were also the targets of compounds present in XXXT. Subsequently, GO function and KEGG pathway enrichment and PPI network analyses revealed that, of the 95 targets and 20 pathways influenced by 20 ingredients in XXXT, 20 targets were associated with patient survival, and XXXT could exert an inhibitory action on the PI3K-AKT signaling pathway. Moreover, XXXT restrained the proliferation of A549 and H460 cells in a concentration-dependent manner and suppressed the mRNA and protein levels of key targets CCNA2, FOSL2, and BIRC5 closely linked to the PI3K-AKT pathway. Hence, XXXT has the potential to improve therapy for NSCLC by targeting the PI3K-AKT signaling pathway.

Highlights

Lung cancer is the major cause of cancer-related deaths all over the world, which lies behind almost one-quarter of all cancer deaths [1, 2]
Screening of the Putative Targets of Non-small cell lung cancer (NSCLC) and PPI Network Construction. e disease targets related to NSCLC were predicted by integrating multisource databases, containing erapeutic Target Database (TTD, https://db.idrblab.org/ttd/) [17], GeneCards database [18], DrugBank database [19], and DisGeNET database [20]. e bioinformatics server was used to generate Venn diagrams of drug and disease targets, and the targets were identified as potential therapeutic targets of XXXT against NSCLC. e protein-protein interaction (PPI) network was established by searching the STRING Database [21]
10 terms were selected with false discovery rate (FDR)

Summary

Introduction

Lung cancer is the major cause of cancer-related deaths all over the world, which lies behind almost one-quarter of all cancer deaths [1, 2]. Non-small cell lung cancer (NSCLC) is the main subtype of lung cancer, and its proportion is approximately 80% in all lung cancer cases. E propensity for recurrence and distant metastasis of NSCLC leads to poor prognosis [3]. It is worth noting that recurrence and metastasis occur following target therapy and recent immunotherapy [4, 5]. Some conventional therapies are accompanied by serious side effects, reducing the life quality of patients [6]. It has been reported that XXXT or its active ingredients exert antiproliferative effects on a variety of tumor cells [9,10,11,12,13,14]. The active components of XXXT and their molecular mechanisms on NSCLC are yet to be determined

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