去甲肾上腺素通过肿瘤相关成纤维细胞促进肺癌A549细胞增殖迁移

Norepinephrine promotes proliferation and migration of lung cancer A549 cells through CAFs

目的研究去甲肾上腺素(norepinephrine,NE)在调控肿瘤相关成纤维细胞(cancer-associated fibroblasts,CAFs)促进肺癌细胞增殖迁移中的作用。方法培养原代CAFs和肺癌A549细胞,RT-PCR和蛋白质印迹检测NE干预后肿瘤相关成纤维细胞VEGF、IL-6和IL-8表达,并检测NE对共培养的CAFs和肺癌A549细胞中E-cadherin和Vimentin表达的影响,细胞划痕实验验证NE促进肺癌A549细胞的迁移能力。结果NE可诱导CAFs VEGF、IL-8和IL-6的高表达,并呈浓度依赖性。β肾上腺素受体抑制剂普萘诺尔PROP可抑制CAFs表达VEGF、IL-8和IL-6;NE可抑制与CAFs共培养的肺癌A549细胞E-cadherin表达,并促进Vimentin上调,增强A549细胞的迁移能力。结论NE通过CAFs协同促进肺癌A549细胞增殖迁移能力。

Aim To study the role of norepinephrine in regulating cancer-associated fibroblasts to promote the proliferation and migration of lung cancer cells.Methods Primary cancer-associated fibroblasts and lung cancer A549 cells were cultured.RT-PCR and Western blotting were used to detect the expression of VEGF,IL-6 and IL-8 in cancer-associated fibroblasts after norepinephrine intervention,and the effect of norepinephrine on the expression of E-cadherin and vimentin in co-cultured CAFs and lung cancer A549 cells were evaluated,and scratching experiments were used to verify that norepinephrine promoted the migration of lung cancer A549 cells.Results Norepinephrine induced the high expression of VEGF,IL-8 and IL-6 in CAFs cells in a concentration-dependent manner.β-adrenergic inhibitor(propranol)could inhibit the expression of VEGF,IL-8 and IL-6 in CAFs cells.Norepinephrine could inhibit the expression of E-cadherin in lung cancer A549 cells co-cultured with CAFs,promote the upregulation of vimentin,and enhance the migration ability of A549 cells.Conclusion Norepinephrine promotes the proliferation and migration of lung cancer A549 cells through CAFs.