| 万海军,邱水玮,陈 霖.粉防己碱通过NF-κB通路抑制肿瘤相关成纤维细胞分泌IL-8阻断肺腺癌细胞的侵袭转移[J].肿瘤学杂志,2020,26(5):402-406. |
| 粉防己碱通过NF-κB通路抑制肿瘤相关成纤维细胞分泌IL-8阻断肺腺癌细胞的侵袭转移 |
| Tetrandrine Inhibits Invasion and Metastasis of Lung Adenocarcinoma Cells by Inhibiting IL-8 Secretion in Tumor-Associated Fibroblasts via NF-κB Pathway |
| 投稿时间：2019-11-18 |
| DOI：10.11735/j.issn.1671-170X.2020.05.B007 |
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| 中文关键词: 粉防己碱 NF-κB通路 肿瘤相关成纤维细胞 肺腺癌 侵袭转移 |
| 英文关键词:tetrandrine NF-κB pathway cancer associated fibroblasts lung adenocarcinoma invasion and metastasis |
| 基金项目:浙江省中医药科学研究基金（2015ZA216）；衢州市指导性科技项目（2016068）；衢州市指导性科技项目（2018071） |
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| 中文摘要: |
| 摘 要：［目的］ 研究粉防己碱（tetrandrine，Tet）通过调控肿瘤相关成纤维细胞（CAF）旁分泌因子的表达抑制肺腺癌细胞侵袭转移的作用效应，探讨NF-κB通路在Tet抑制CAF分泌IL-8促进肺腺癌细胞侵袭转移中的重要作用。［方法］ 采用条件培养基（CM）刺激胚肺成纤维细胞MRC5建立CAF模型，Western blot实验分析Tet作用前后NF-κB通路蛋白IKK、IκB和p65表达和磷酸化水平，ELISA实验检测Tet作用前后CAF分泌IL-8情况，以及Tet对CAF诱导肺腺癌细胞H1975侵袭转移的影响。抗体封闭培养基中游离的IL-8，分析CAF诱导H1975细胞侵袭转移能力的变化，验证IL-8是否Tet调控CAF旁分泌因子的表达抑制H1975细胞侵袭转移的关键因子。［结果］ Tet作用24h，CAF中NF-κB通路蛋白IKK、IκB和p65蛋白的磷酸化水平显著性下降；Tet组培养基上清液中IL-8含量为（151.7±24.8）pg/ml，显著性低于模型组的（384.7±39.5）pg/ml（P<0.001）；模型组诱导H1975细胞迁移的数量为141.7±21.5，Tet组为41.3±11.9（P<0.01）；模型组诱导H1975细胞侵袭的数量为129.7±25.1，Tet组为56.7±14.5（P<0.05）。模型组诱导H1975细胞迁移的数量为152.3±25.5，IL-8封闭（aIL-8）组为61.7±15.5（P<0.01）；模型组诱导H1975细胞侵袭的数量为136.3±14.5，aIL-8组为73.3±12.7（P<0.01）。［结论］ Tet具有抑制CAF诱导肺腺癌细胞侵袭转移的作用效应，其机制与抑制NF-κB通路的活性和CAF分泌IL-8有关。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the inhibitory effect of tetrandrine(Tet) on the invasion and metastasis of lung adenocarcinoma cells and its mechanisms. ［Methods］ The conditioned medium(CM) was used to stimulate embryonic lung fibroblasts MRC5 to establish a cancer-associated fibroblast(CAF) model. Western blot was used to analyze the expression and phosphorylation level of NF-κB pathway proteins IKK，IκB and p65 before and after Tet treatment. ELISA assay was used to assess the secretion of IL-8 in CAF，and the ability of CAF to induce the invasion and metastasis of human lung adenocarcinoma H1975 cells was analyzed with Transwell assay. The free IL-8 in the culture medium was blocked by antibody(aIL-8 group)，and the change of CAF induced effect was evaluated in H1975 cells. ［Results］ After 24h of Tet treatment，the phosphorylation levels of NF-κB pathway proteins IKK，IκB，and p65 protein in CAF decreased significantly. The content of IL-8 in the supernatant of the Tet group was(151.7±24.8) pg/ml，which was significantly lower than the model group(384.7±39.5) pg/ml(P<0.001). The number of H1975 cell migration in the model group was 141.7±21.5，and that in Tet group was 41.3±11.9(P<0.01). The number of H1975 cell invasion in the model group was 129.7±25.1，and that in Tet group was 56.7±14.5(P<0.05). The number of H1975 cell migration induced by the model group was 152.3±25.5，and that of the IL-8 blocked(aIL-8) group was 61.7±15.5(P<0.01). The number of H1975 cells in the model group was 136.3±14.5，and It was 73.3±12.7 in the aIL-8 group(P<0.01). ［Conclusion］ Tetrandrine can inhibit the CAF-induced invasion and metastasis of lung adenocarcinoma cells，which is associated with the inhibition of the activity of NF-κB pathway and the secretion of IL-8 by CAF. |
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