干旱区生态环境知识资源中心(Arid): Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer

Arid

DOI	10.1186/s12906-024-04347-y
	Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer
	Lee, Kangwook; Choi, Yu-Jeong; Lim, Hae-In; Cho, Kwang Jin; Kang, Nuri; Ko, Seong-Gyu
通讯作者	Ko, SG
来源期刊	BMC COMPLEMENTARY MEDICINE AND THERAPIES
EISSN	2662-7671
出版年	2024
卷号	24 期号:1
英文摘要	Background Non-small cell lung cancer (NSCLC) is one of the leading causes of human death worldwide. Herbal prescription SH003 has been developed to treat several cancers including NSCLC. Due to the multi-component nature of SH003 with multiple targets and pathways, a network pharmacology study was conducted to analyze its active compounds, potential targets, and pathways for the treatment of NSCLC. Methods We systematically identified oral active compounds within SH003, employing ADME criteria-based screening from TM-MC, OASIS, and TCMSP databases. Concurrently, SH003-related and NSCLC-associated targets were amalgamated from various databases. Overlapping targets were deemed anti-NSCLC entities of SH003. Protein-protein interaction networks were constructed using the STRING database, allowing the identification of pivotal proteins through node centrality measures. Empirical validation was pursued through LC-MS analysis of active compounds. Additionally, in vitro experiments, such as MTT cell viability assays and western blot analyses, were conducted to corroborate network pharmacology findings. Result We discerned 20 oral active compounds within SH003 and identified 239 core targets shared between SH003 and NSCLC-related genes. Network analyses spotlighted 79 hub genes, including TP53, JUN, AKT1, STAT3, and MAPK3, crucial in NSCLC treatment. GO and KEGG analyses underscored SH003's multifaceted anti-NSCLC effects from a genetic perspective. Experimental validations verified SH003's impact on NSCLC cell viability and the downregulation of hub genes. LC-MS analysis confirmed the presence of four active compounds, namely hispidulin, luteolin, baicalein, and chrysoeriol, among the eight compounds with a median of > 10 degrees in the herb-compounds-targets network in SH003. Previously unidentified targets like CASP9, MAPK9, and MCL1 were unveiled, supported by existing NSCLC literature, enhancing the pivotal role of empirical validation in network pharmacology. Conclusion Our study pioneers the harmonization of theoretical predictions with practical validations. Empirical validation illuminates specific SH003 compounds within NSCLC, simultaneously uncovering novel targets for NSCLC treatment. This integrated strategy, accentuating empirical validation, establishes a paradigm for in-depth herbal medicine exploration. Furthermore, our network pharmacology study unveils fresh insights into SH003's multifaceted molecular mechanisms combating NSCLC. Through this approach, we delineate active compounds of SH003 and target pathways, reshaping our understanding of its therapeutic mechanisms in NSCLC treatment.
英文关键词	Network pharmacology Non-small cell lung cancer SH003 Gene ontology KEGG
类型	Article
语种	英语
开放获取类型	gold, Green Published
收录类别	SCI-E
WOS记录号	WOS:001155946800002
WOS关键词	BREAST-CANCER ; ADENOCARCINOMA CELLS ; MESENCHYMAL TRANSITION ; 1ST-LINE IMMUNOTHERAPY ; INDUCED APOPTOSIS ; DRUG DISCOVERY ; GENE ONTOLOGY ; LUTEOLIN ; INHIBITION ; CARCINOMA
WOS类目	Integrative & Complementary Medicine
WOS研究方向	Integrative & Complementary Medicine
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/403043
推荐引用方式 GB/T 7714	Lee, Kangwook,Choi, Yu-Jeong,Lim, Hae-In,et al. Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer[J],2024,24(1).
APA	Lee, Kangwook,Choi, Yu-Jeong,Lim, Hae-In,Cho, Kwang Jin,Kang, Nuri,&Ko, Seong-Gyu.(2024).Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer.BMC COMPLEMENTARY MEDICINE AND THERAPIES,24(1).
MLA	Lee, Kangwook,et al."Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer".BMC COMPLEMENTARY MEDICINE AND THERAPIES 24.1(2024).