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

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.

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Parthenolide Augments the Chemosensitivity of Non-small-Cell Lung Cancer to Cisplatin via the PI3K/AKT Signaling Pathway

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2020.610097 ◽

2021 ◽

Vol 8 ◽

Author(s):

Li-Mei Wu ◽

Xiao-Zhong Liao ◽

Yan Zhang ◽

Zi-Rui He ◽

Shi-Qing Nie ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Signaling Pathway ◽

Cell Lung Cancer ◽

Caspase 3 ◽

Akt Signaling ◽

Small Cell ◽

Dependent Manner ◽

Akt Signaling Pathway ◽

Small Cell Lung

The mortality rate of non-small-cell lung cancer (NSCLC) remains high worldwide. Although cisplatin-based chemotherapy may greatly enhance patient prognosis, chemotherapy resistance remains an obstacle to curing patients with NSCLC. Therefore, overcoming drug resistance is the main route to successful treatment, and combinatorial strategies may have considerable clinical value in this effort. In this study, we observed that both parthenolide (PTL) and cisplatin (DDP) inhibited the growth of NSCLC cells in a dose- and time-dependent manner. The combination of PTL and DDP presented a synergistic inhibitory effect on NSCLC at a ratio of 50:1. The combination of PTL and DDP synergistically inhibited cell migration and invasion, inhibited cell cycle progression, and induced apoptosis of A549 and PC9 cells. Bioinformatics and network pharmacology analysis indicated that PTL may primarily affect the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. After treatment with PTL and DDP either alone or in combination, Western blot analysis revealed that the proteins levels of Bax and cleaved Caspase-3 were upregulated, while p-PI3K, p-Akt, Caspase-3, and Bcl-2 proteins were downregulated. Among these alterations, the combination of PTL and DDP was found to exhibit the most significant effects. PTL might therefore be considered as a new option for combination therapy of NSCLC.

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