Alginic acid inhibits non-small cell lung cancer-induced angiogenesis via activating miR-506 expression

Angiogenesis is a key event in non-small cell lung cancer progression. Alginic acid (AA), a kind of naturally occurring polyuronic acid, is generally enriched in edible brown algae. Recent studies have uncovered its anti-anaphylactic and anti-inflammatory properties. However, the effects of AA on human malignancies remain unknown. Herein, efficient inhibition of AA on NSCLC-induced angiogenesis was observed with tube formation and xenograft models. Subsequent results indicated that AA downregulated the expression of VEGF-A, a key angiogenesis-inducing cytokine. In addition, AA downregulated STAT3, a transcriptional inducer of VEGF-A and increased non-coding RNA miR-506 expression, respectively. Furthermore, miR-506 directly modulated STAT3 relying on base pairing the 3′-UTR in STAT3 mRNA. We also found that abrogation of miR-506 abolished the inhibitory effect of AA on VEGF-A expression and NSCLC-induced angiogenesis. Finally, xenografts experiments also showed that oral administration of AA could significantly attenuate NSCLC angiogenesis, indicated by decreased micro-vessel density (MVD) and the MVD marker CD31 expression in xenografts tissues. Correspondingly, AA treatment also downregulated VEGF-A, STAT3 and increased miR-506 expression in xenografts samples, respectively. Taken together, these results suggested that AA could suppress NSCLC-induced angiogenesis via miR-506/STAT3/VEGF-A axis. .