Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments.

ETHNOPHARMACOLOGICAL RELEVANCE: Jinfu'an Decoction (JFAD) is a traditional Chinese decoction used in lung cancer treatment to improve patient quality of life and survival. Previous research has established that JFAD has a significant therapeutic effect on non-small cell lung cancer (NSCLC), although the underlying molecular mechanisms have not been largely underexplored. AIM OF THE STUDY: We used network pharmacology to identify the putative active ingredients of JFAD and conducted experimental studies to determine the potential molecular mechanism of JFAD in NSCLC treatment. MATERIALS AND METHODS: The herbal components in JFAD-containing serum were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS), and targets associated with the anti-lung cancer metastasis effects of JFAD were retrieved from various databases. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Next, the protein-protein interactions network and the "JFAD-Chemical Component-Target-KEGG Pathway" network were constructed. The network pharmacology findings were confirmed by in vitro and in vivo experiments. In vitro experiments were conducted to assess cell viability by CCK8 assay, cell cycle analysis by propidium iodide (PI) assay, and migration and invasion ability of cells by the transwell assay. In vivo experiments were performed to assess the efficacy of JFAD on the tumor by observing the growth of transplanted tumor models in nude mice and evaluated by in vivo bioluminescence imaging. Moreover, we assessed the effect of JFAD on the PI3K/Akt signaling pathway and proteins of Lumican, p120ctn, and specific RhoGTP enzyme family members (RhoA, Rac1, and RhoC) by Western Blot and immunohistochemistry. RESULTS: 32 herbal components were identified in the JFAD-containing serum, which potentially acted on 229 targets related to lung cancer metastasis. Network pharmacology results suggested that JFAD may treat lung cancer metastasis by targeting the PI3K/Akt pathway via regulating multiple core targets. Our experiments showed that JFAD suppressed the proliferation of A549 cells in vitro, induced cell cycle arrest, and reduced the migration and invasion ability of A549 cells. Our in vivo study revealed that JFAD inhibited tumor growth in a nude mouse model. Additionally, we found that JFAD could downregulate the expression of the PI3K/Akt pathway and affect the expression of Lumican, p120ctn, and specific RhoGTPase family members. CONCLUSIONS: In conclusion, through network pharmacology, we have unveiled the underlying mechanisms that link the various components, targets, and pathways influenced by JFAD in the context of lung cancer metastasis. Our experimental results suggest that the oncostatic effects of JFAD may be achieved by upregulating the expression of Lumican/p120ctn and downregulating the levels of specific RhoGTPase family members, which in turn block the PI3K/Akt signaling pathway.

Development and validation of an immune-related gene signature for prognosis in Lung adenocarcinoma.

The most common type of lung cancer tissue is lung adenocarcinoma. The TCGA-LUAD cohort retrieved from the TCGA dataset was considered the internal training cohort, while GSE68465 and GSE13213 datasets from the GEO database were used as the external test cohort. The TCGA-LUAD cohort was classified into two immune subtypes using single-sample gene set enrichment analysis of the immune gene set and unsupervised clustering analysis. The ESTIMATE algorithm, the CIBERSORT algorithm, and HLA family expression levels again validated the reliability of this typing. We performed Venn analysis using immune-related genes from the immport dataset and differentially expressed genes from the subtypes to retrieve differentially expressed immune genes (DEIGs). In addition, DEIGs were used to construct a prognostic model with the least absolute shrinkage and selection operator regression analysis. A reliable risk model consisting of 11 DEIGs, including S100P, INHA, SEMA7A, INSL4, CD40LG, AGER, SERPIND1, CD1D, CX3CR1, SFTPD, and CD79A, was then built, and its reliability was further confirmed by ROC curve and calibration plot analysis. The high-risk score subgroup had a poor prognosis and a lower tumour immune dysfunction and exclusion score, indicating a greater likelihood of anti-PD-1/cytotoxic T lymphocyte antigen 4 benefit.

The effectiveness of blood-activating and stasis-transforming traditional Chinese medicines (BAST) in lung cancer progression-a comprehensive review.

ETHNOPHARMACOLOGICAL RELEVANCE: Blood-activating and stasis-transforming traditional Chinese medicines (BAST) are a class of herbs that have the effect of dilating blood vessels and dispersing stagnation. Modern pharmaceutical research has demonstrated that they are capable of improving hemodynamics and micro-flow, resist thrombosis and promote blood flow. BAST contain numerous active ingredients, which can theoretically regulate multiple targets at the same time and have a wide range of pharmacological effects in the treatment of diseases including human cancers. Clinically, BAST have minimal side effects and can be used in combination with Western medicine to improve patients' quality of life, lessen adverse effects and minimize the risk of recurrence and metastasis of cancers. AIM OF THE REVIEW: We aimed to summarize the research progression of BAST on lung cancer in the past five years and present a prospect for the future. Particularly, this review further analyzes the effects and molecular mechanisms that BAST inhibit the invasion and metastasis of lung cancer. MATERIALS AND METHODS: Relevant studies about BSAT were collected from PubMed and Web of science. RESULTS: Lung cancer is one of the malignant tumors with the highest mortality rate. Most patients with lung cancer are diagnosed at an advanced stage and are highly susceptible to metastasis. Recent studies have shown that BAST, a class of traditional Chinese medicine (TCM) with the function of opening veins and dispersing blood stasis, significantly improve hemodynamics and microcirculation, prevent thrombosis and promote blood flow, and thereby inhibiting the invasion and metastasis of lung cancer. In the current review, we analyzed 51 active ingredients extracted from BAST. It was found that BAST and their active ingredients contribute to the prevention of invasion and metastasis of lung cancer through multiple mechanisms, such as regulation of EMT process, specific signaling pathway and metastasis-related genes, tumor blood vessel formation, immune microenvironment and inflammatory response of tumors. CONCLUSIONS: BSAT and its active ingredients have showed promising anticancer activity and significantly inhibit the invasion and metastasis of lung cancer. A growing number of studies have realized their potential clinical significance in the therapy of lung cancer, which will provide substantial evidences for the development of new TCM for lung cancer therapy.

Multi-omics analysis reveals the prognostic and tumor micro-environmental value of lumican in multiple cancer types.

Background: Lumican (LUM), a proteoglycan of the extracellular matrix, has been reported to be involved in the regulation of immune escape processes, but the data supporting this phenomenon are not sufficient. In this study, we aimed to explore the links among LUM expression, survival, tumor microenvironment (TME), and immunotherapy in 33 cancer types. Methods: Data from several databases, such as UCSC Xena, GTEx, UALCAN, HPA, GEPIA2, TISIDB, PrognoScan, TIMER2, and GEO, as well as published studies, were used to determine the relationship between LUM expression and clinical features, TME, heterogeneity, and tumor stemness. Results: The expression of LUM was statistically different in most tumors versus normal tissues, both at the RNA and protein expression levels. High expression of LUM was typically associated with a poor prognosis in tumors. Additionally, immune scores, six immune cells, four immunosuppressive cells, cancer-associated fibroblasts (CAFs)-associated and immunosuppressive factors, tumor mutation burden (TMB), microsatellite instability (MSI), DNAss, and RNAss were all significantly associated with LUM. Among them, LUM expression displayed a significant positive correlation with CAFs and their factors, and exhibited immunosuppressive effects in six independent immunotherapy cohorts. Conclusion: Multi-omics analysis suggests that LUM may have been a prognostic marker, contributed to immunosuppression in the TME, and decreased the effectiveness of immune checkpoint inhibitors.

A Data Mining-Based Analysis of Core Herbs on Different Patterns (Zheng) of Non-Small Cell Lung Cancer.

OBJECTIVE: To explore the role of Chinese prescriptions in non-small cell lung cancer (NSCLC) and provide references for the application of herbs and prescriptions. METHODS: Randomized and quasirandomized controlled clinical trials on Chinese herbal medicine in the treatment of NSCLC were collected from seven databases to establish a database of prescriptions on NSCLC. Data-mining analyses were performed by RStudio (v4.0.3) software. RESULTS: A total of 970 prescriptions were obtained from 945 included studies, involving 7 syndromes and 428 herbs. The main patterns of NSCLC included qi deficiency pattern, yin deficiency pattern, blood deficiency pattern, kidney deficiency pattern, heat toxin pattern, phlegm-dampness pattern, and blood stasis pattern. High-frequency herbs on NSCLC were Astragali Radix (Huangqi), Atractylodis Macrocephalae Rhizome (Baizhu), Glycyrrhizae Radix Rhizome (Gancao), Poria (Fuling), Ophiopogonis Radix (Maidong), Hedyotidis Diffusae Herba (Baihuasheshecao), Codonopsis Radix (Dangshen), and Glehniae Radix (Beishashen). The properties of the herbs were mainly cold, warm, and mild. The flavors of the herbs were mainly sweet, bitter, and pungent. The main meridian tropisms were Lung Meridian of Hand-Taiyin, Spleen Meridian of Foot-Taiyin, and Stomach Meridian of Foot-Yangming. CONCLUSION: Applying clearing and tonifying method by targeting the lung and spleen was the most frequently used therapy in the treatment of NSCLC. This study offered a glimpse of unique views of traditional Chinese medicine on NSCLC and may benefit the treatment of NSCLC.