ReferenceID 4955

Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish

Phytomedicine

Background: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the

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Reference Id
4955
Evidence Id
21545
Core Evidence Id
21545
Source Reference Id
3163
Herb2 Reference Id
HBREF003960
Subject Paper Key
HBIN021460_36610112
Pubmed Id
36610112
Doi
10.1016/j.phymed.2022.154613
Paper Title
Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish
Paper Abstract
Background: Small cell lung cancer (SCLC) is an aggressive tumor with high brain metastasis (BM) potential. There has been no significant progress in the treatment of SCLC for more than 30 years. Cordycepin has shown the therapeutic potential for cancer by modulating multiple cellular signaling pathways. However, the effect and mechanism of cordycepin on anti-SCLC BM remain unknown. Purpose: In this study, we focused on the anti-SCLC BM effect of cordycepin in the zebrafish model and its potential mechanism. Study design and methods: A SCLC xenograft model based on zebrafish embryos and in vitro cell migration assay were established. Cordycepin was administrated by soaking and microinjection in the zebrafish model. RNA-seq assay was performed to analyze transcriptomes of different groups. Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to reveal the underlying mechanism. Real-time qPCR was used to verify the effects of cordycepin on the key genes. Results: Cordycepin showed lower cytotoxicity in vitro compared with cisplatin, anlotinib and etoposide, but showed comparable anti-proliferation and anti-BM effects in zebrafish SCLC xenograft model. Cordycepin showed significant anti-SCLC BM effects when administrated by both soaking and microinjection. RNA-seq demonstrated that cordycepin was involved in vitamin D metabolism, lipid transport, and proteolysis in cellular protein catabolic process pathways in SCLC BM microenvironment in zebrafish, and was involved in regulating the expressions of key genes such as cyp24a1, apoa1a, ctsl. The anti-BM effect of cordycepin in SCLC was mediated by reversing the expression of these genes. Conclusion: Our work is the first to describe the mechanism of cordycepin against SCLC BM from the perspective of regulating the brain microenvironment, providing new evidence for the anti-tumor effect of cordycepin.
Journal
Phytomedicine
Publish Year
2023
Experiment Subject
zebrafish
Experiment Type
Animal Experiment
Phenotype Related
Small Cell Lung Cancer; Anti-sclc; Tumor; Cancer; High Brain Metastasis
Paper Title Cn
Paper Title En
Efficacy and mechanism study of cordycepin against brain metastases of small cell lung cancer based on zebrafish
Bilingual Status
semi_complete