Department of Thoracic Surgery, Nanjing Chest Hospital, Nanjing Medical University Affiliated Brain Hospital (Thoracic Academy), No.215, Guangzhou Road, Gulou District, Nanjing, 210029, People's Republic of China.
J Nat Med. 2021 Jun;75(3):553-564. doi: 10.1007/s11418-021-01493-2. Epub 2021 Mar 5.
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. .
血管生成是非小细胞肺癌进展的关键事件。褐藻酸（AA）是一种天然存在的聚多糖酸，通常富含于食用褐藻中。最近的研究揭示了其抗过敏性和抗炎性特性。然而，AA 对人类恶性肿瘤的影响尚不清楚。在此，我们观察到 AA 对 NSCLC 诱导的血管生成具有高效的抑制作用，表现在管形成和异种移植模型中。随后的结果表明，AA 下调了 VEGF-A 的表达，VEGF-A 是一种关键的血管生成诱导细胞因子。此外，AA 下调了 STAT3 的表达，STAT3 是 VEGF-A 的转录诱导因子，同时增加了非编码 RNA miR-506 的表达。此外，miR-506 通过与 STAT3 mRNA 的 3'UTR 碱基配对直接调节 STAT3。我们还发现，miR-506 的缺失消除了 AA 对 VEGF-A 表达和 NSCLC 诱导的血管生成的抑制作用。最后，异种移植实验也表明，AA 的口服给药可以显著减弱 NSCLC 的血管生成，表现为异种移植组织中微血管密度（MVD）和 MVD 标志物 CD31 表达的降低。相应地，AA 处理也分别下调了异种移植样本中的 VEGF-A、STAT3 和增加了 miR-506 的表达。综上所述，这些结果表明 AA 可以通过 miR-506/STAT3/VEGF-A 轴抑制 NSCLC 诱导的血管生成。
