期刊
PHYTOMEDICINE
卷 89, 期 -, 页码 -出版社
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2021.153601
关键词
Mucinous adenocarcinoma; Resveratrol; SPDEF; MUC5AC; Chemosensitivity
资金
- Clinical specialty construction plan of Health Commission of Putuo District [2020tszk02]
- Shanghai Science and Technology Committee [18140904001,17401970900,20ZR1450400]
- Research project of Shanghai Sixth People's Hospital Joint Construction of Scientific [20-LY-03]
- Scientific Foundation of Putuo Hospital [2017206A]
The study revealed that Res decreased the expression of MUC5AC in mucus-producing A549 human lung carcinoma cells in an SPDEF-dependent manner, with a simultaneous decrease in ERK expression and AKT pathway activation. SPDEF was found to be overexpressed in lung adenocarcinoma, particularly in mucinous adenocarcinoma, and Res treatment increased the sensitivity of A549 cells to cisplatin by inhibiting the SPDEF-MUC5AC axis.
Background: MUC5AC was recently identified to play important roles in the proliferation and metastasis of malignant mucinous lung tumor cells. Resveratrol (Res), a natural compound with anticancer effects in lung cancer cells, has been reported to inhibit mucin production in airway epithelial cells. This study aimed to investigate the inhibitory effect of Res on MUC5AC expression in lung mucinous adenocarcinoma cells and the potential mechanisms. Methods: Mucus-producing A549 human lung carcinoma cells were used to test the effects of Res on SPDEF and MUC5AC expression. Gene and protein expression was assessed by real-time quantitative PCR (qPCR), immunofluorescence and western blotting assays. SPDEF lentivirus was used to upregulate SPDEF expression levels in mucus-producing A549 human lung carcinoma cells. Cell proliferation was assessed by Cell Counting Kit-8 (CCK8) assay. Results: Res decreased MUC5AC expression in an SPDEF-dependent manner in mucus-producing A549 human lung carcinoma cells, and this change was accompanied by decreased ERK expression and AKT pathway activation. Moreover, SPDEF was found to be overexpressed in lung adenocarcinoma (LUAD), especially in mucinous adenocarcinoma. In-vitro functional assays showed that overexpression of SPDEF reduced the chemosensitivity of A549 cells to cisplatin (DDP). In addition, Res treatment increased A549 cell chemosensitivity to DDP by inhibiting the SPDEF-MUC5AC axis. Conclusion: Our results indicate that the SPDEF-MUC5AC axis is associated with DDP sensitivity, and that Res decreases SPDEF and MUC5AC expression by inhibiting ERK and AKT signaling in A549 cells, which provides a potential pharmacotherapy for the prevention and therapeutic management of mucinous adenocarcinoma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据