木犀草素抑制非小细胞肺癌(NSCLC)的肿瘤发生,但其机制仍有待澄清。我们在此探索木犀草素在NSCLC血管内皮细胞(NSCLC-VECs)中的作用。在提取和鉴定NSCLC-VECs后,用木犀草素处理细胞并转染。生存能力,迁移,测量细胞的血管生成和侵袭。miR-133a-3p的水平,富含嘌呤的元素结合蛋白B(PURB),血管内皮生长因子(VEGF),磷脂酰肌醇3-激酶(PI3K),Akt,丝裂原活化蛋白激酶(MAPK),测定基质金属蛋白酶(MMP)-2/-9。鉴定了miR-133a-3p与PURB的相互作用关系。木犀草素抑制生存力,迁移,NSCLC-VECs的血管生成和侵袭,但上调miR-133a-3p水平,而miR-133a-3p抑制剂抵消木犀草素对生存力的抑制作用,迁移,血管生成,NSCLC-VECs的侵袭。木犀草素抑制迁移和侵袭相关蛋白的表达(VEGF,MMP-2和MMP-9),PI3K/Akt和MAPK信号通路相关因子,而miR-133a-3p抑制剂逆转木犀草素对NSCLC-VECs的抑制作用。木犀草素降低PURB的水平,miR-133a-3p靶向。ShPURB促进NSCLC-VECs中miR-133a-3p水平,在逆转miR-133a-3p抑制剂对迁移的促进作用的同时,入侵,以及迁移和入侵相关蛋白的水平,NSCLC-VECs中PI3K/Akt和MAPK通路相关因子。总的来说,木犀草素通过miR-133a-3p/PURB介导的MAPK和PI3K/Akt通路抑制NSCLC-VECs的迁移和侵袭。
Luteolin inhibits tumorigenesis of non-small cell lung cancer (NSCLC), but its mechanism still needs to be clarified. We hereby explored the effects of luteolin in vascular endothelial cells of NSCLC (NSCLC-VECs). After extraction and identification of NSCLC-VECs, cells were treated with luteolin and transfected. The viability, migration, angiogenesis and invasion of the cells were measured. The levels of miR-133a-3p, purine rich element binding protein B (
PURB), vascular endothelial growth factor (VEGF), phosphatidylinositol 3-kinase (PI3K), Akt, mitogen-activated protein kinases (MAPK), matrix metalloproteinase (MMP)-2/-9 were determined. The interaction relationship of miR-133a-3p and
PURB was identified. Luteolin inhibited the viability, migration, angiogenesis and invasion of NSCLC-VECs yet up-regulated miR-133a-3p level, while miR-133a-3p inhibitor counteracted the repressive effect of luteolin on the viability, migration, angiogenesis, and invasion in NSCLC-VECs. Luteolin inhibited the expressions of migration- and invasion-associated proteins (VEGF, MMP-2 and MMP-9), PI3K/Akt and MAPK signaling pathways-related factors, while miR-133a-3p inhibitor reversed the inhibitory effect of Luteolin on NSCLC-VECs. Luteolin decreased the level of
PURB, which was targeted by miR-133a-3p. ShPURB promoted miR-133a-3p level in NSCLC-VECs, while reversing the promoting effects of miR-133a-3p inhibitor on the migration, invasion, and levels of migration- and invasion-associated proteins, PI3K/Akt and MAPK pathways-associated factors in NSCLC-VECs. Collectively speaking, luteolin inhibits the migration and invasion of NSCLC-VECs via miR-133a-3p/
PURB- mediated MAPK and PI3K/Akt pathways.