Background: ADAMTS-1 (a disintegrin and metalloproteinase with thrombospondin repeats-1) is a recently characterized protein containing a metalloproteinase domain, a disintegrin-like domain and a thrombospondin type 1 motif, which is involved in angiogenesis. However, the roles of ADAMTS-1 in angiogenesis of lung cancer (LC) remain unclear.Methods: The mRNA expression of ADAMTS-1 and VEGF was examined by qRT-PCR. Western blots were used to detect the protein expression of ADAMTS-1 and vascular endothelial growth factor (VEGF) in A549 cells and to analyse the cellular effect of a PI3K/Akt activator and an endothelial nitric oxide synthase (eNOS) activator. ADAMTS-1 and VEGF contents in cell culture supernatants were measured by ELISA.Cell viability, cell cycle, migration, and angiogenesis of HUVECs were evaluated by MTT assay, flow cytometry, scratch assay and tube formation assay, respectively.Results: Our data revealed that the expression of ADAMTS-1 was downregulated, while the expression of VEGF was upregulated in A549 cells. Decreased ADAMTS-1 content was also detected in A549 cell culture supernatant. Overexpression of ADAMTS-1 inhibited VEGF expression and A549 cell proliferation.Moreover, ADAMTS-1 overexpression repressed proliferation, migration and angiogenesis of HUVECs.Mechanistically, ADAMTS-1 suppressed the expression of VEGF in HUVECs by inhibiting PI3K/Akt-eNOS, while a PI3K activator and an eNOS activator each partly reversed the expression of VEGF. In addition, activation of the PI3K/Akt pathway or VEGF overexpression reversed the inhibitory effect of ADAMTS-1 overexpression on HUVECs angiogenesis.Conclusions: These results indicated that ADAMTS-1 inhibited angiogenesis of LC cells via regulation of the PI3K/Akt-eNOS/VEGF axis, which shed light on LC pathogenesis and provided potential targets for LC therapy.
ED combined with DDP could control the tumor growth effectively, and avoid weight loss. ED could reduce VEGF expression, and enhance Sema3A expression. Tumor vessel presents transient normalization. It is easy for DDP perfusion, and to kill tumor cells.
Emerging research has suggested the anticancer potential of tanshinone IIA, the bioactive ingredient isolated from the traditional Chinese herb Salvia miltiorrhiza. However, the molecular mechanism of sodium tanshinone IIA sulfonate (STS) antilung cancer effect is not very clear. In this study, our purpose is to investigate the roles of STS and elongation factor-2 kinase (eEF-2K) in regulating the proliferation, migration, and invasion of A549 cells and explore the implicated pathways. We found that STS suppressed A549 cell survival and proliferation in a time-and xdose-dependent manner. Knockdown of eEF-2K and treatment with STS synergistically exerted antiproliferative, -migratory, and -invasive effects on A549 cells. These effects were caused by attenuation of the extracellular signal-regulated kinase (ERK) pathway via inhibition of tissue transglutaminase (TG2). In summary, the inhibition of eEF-2K synergizes with STS treatment, exerting anticancer effects on lung adenocarcinoma cells through the TG2/ERK signaling pathway, which provides a potential therapeutic target for treating lung adenocarcinoma.
Background and Objective: Lung adenocarcinoma is the most common and aggressive subtype of lung cancer, with the poor overall prognosis. IL2 is one of the earliest cytokines discovered that stimulates lymphocyte proliferation. However, the role of IL2 in LUAD has not been clarified. Methods: UALCAN, The HPA and TIMER database were used to investigate IL2 expression in LUAD. HPA, PrognoScan Database Analysis and Kaplan-Meier plotter database were used to explore the survival curve evaluating the prognostic value of IL2 for LUAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of IL2-interacting genes identified by GeneMANIA database. TIMER was used to analyze the correlation of IL2 and immune cell infiltration or immune checkpoint expression level in LUAD. Results: In present study, the results showed that the expression of IL-2 in lung adenocarcinoma was lower than that in the normal control group by means of bioinformatics analysis of the TIMER, UALCAN and HPA public databases. Moreover, LUAD patients with downregulated IL2 expression exhibited poor overall survival. Besides, IL2 was significantly positively correlated with various immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in LUAD. And IL2 was also markedly positively associated with biomarkers of these infiltrated immune cells. IL2 expression was also positively correlated with PD-1, PD-L1 and CTLA-4 expression. Conclusion: In summary, our results indicate that down-regulation of interleukin-2 predicts poor prognosis and associated with immune escape in LUAD and IL2 could serve as a potential novel prognostic biomarker for LUAD.
Context Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. Objective Our study explores the effect and mechanism of STS against LUAD. Materials and methods LUAD cells were treated with 100 μM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. Results STS significantly decreased the viability (40–50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. Discussion and Conclusions STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.
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