Potential monoamine oxidase A inhibitor suppressing paclitaxel‐resistant non‐small cell lung cancer metastasis and growth

作者：Xiaoguang Yang, Dong‐Xue Zhao, Yanfeng Li, Yanyu Li, Wei Cui, Yuxin Li, Han Li, Xinyu Li, Dun Wang · 发表于：Thoracic Cancer · 年份：2020 · DOI：10.1111/1759-7714.13617 · 被引用次数：17 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Microbial metabolism and enzyme function、Parkinson's Disease Mechanisms and Treatments

BACKGROUND: High expression of monoamine oxidase A (MAOA) in non-small cell lung cancer (NSCLC) is related to epithelial-mesenchymal transition (EMT) and the development of clinicopathological features of NSCLC. Nevertheless, the role of MAOA in drug resistance still remains unclear. Hence, the aim of this article was to evaluate a previously synthesized MAOA inhibitor (G11) on inhibiting paclitaxel-resistant NSCLC metastasis and growth. METHODS: First, MAOA expression level was evaluated in several NSCLC cell lines. An MTT assay was used to validate the inhibitory effect of G11 on NSCLC cells in vitro. Second, gene expression in G11-treated H460/PTX cells was analyzed by microarray gene expression. Third, transwell assay was performed to assess the invasion and metastasis of G11-treated A549/PTX and H460/PTX cells and western blot assay used to analyze vital protein expression level in G11-treated H460/PTX cells. Finally, the antimetastatic effect of G11 was tested in an NSCLC in vivo model. RESULTS: Our data revealed that G11 significantly inhibited the viability of paclitaxel (PTX)-resistant NSCLC cell lines (A549/PTX and H460/PTX). G11 dramatically reduced the expression of MAOA in A549/PTX and H460/PTX cells, which exhibited relatively high MAOA expression levels. Additionally, G11 was found to hinder A549/PTX and H460/PTX cell migration and invasion. Furthermore, the in vivo study indicated that the coadministration of G11 and paclitaxel significantly suppressed tumor m...