Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL6/STAT3 signaling pathway.
Oncol Rep
; 44(3): 1049-1063, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32705271
ABSTRACT
Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis. Shikonin, which is extracted from the Chinese herb Zicao (the dried root of Lithospermum erythrorhizon), possesses various pharmacological effects, but its effect on tumor metastasis in the inflammatory microenvironment remains unknown. In the present study, we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as the underlying molecular mechanisms. It was found that, in the inflammatory microenvironment simulated by THP1 cell conditioned medium (THP1CM) in vitro, shikonin significantly inhibited the epithelialmesenchymal transition (EMT), migration and invasion of human lung adenocarcinoma cell lines A549 and H1299. In addition, we found that interleukin6 (IL6), which is expressed in THP1CM, promoted the EMT of lung adenocarcinoma cells, and shikonin markedly inhibited IL6induced EMT and cell motility. Moreover, shikonin inhibited IL6induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), prevented phosphorylated STAT3 (pSTAT3) translocation into the nucleus, and suppressed pSTAT3 transactivation activity. Additionally, it was found that shikonin inhibited lung metastasis, EMT and expression of pSTAT3 of A549 cells in vivo. Furthermore, IL6 levels in human lung adenocarcinoma tissues were significantly associated with tumornodemetastasis stage and lymph node metastasis, and its expression was correlated with tumorassociated macrophage (TAM) infiltration. Together, these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL6/STAT3 signaling pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
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2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Naftoquinonas
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Adenocarcinoma de Pulmão
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Neoplasias Pulmonares
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Metástase Linfática
Tipo de estudo:
Observational_studies
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Prognostic_studies
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Oncol Rep
Ano de publicação:
2020
Tipo de documento:
Article