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

Lung Cancer
02/09/2020

Thorac Cancer. 2020 Sep 2. doi: 10.1111/1759-7714.13617. Online ahead of print.

ABSTRACT

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 metastasis in H460/PTX lung metastasis models.

CONCLUSIONS: These findings indicated G11 showed a moderate inhibitory effect on paclitaxel-resistant NSCLC metastasis and growth, and support further investigation on MAOA potentially as a promising therapeutic target for paclitaxel-resistant NSCLC treatment.


KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Inhibition of MAOA might contribute to the suppression of metastasis and growth in PTX-resistant NSCLC cells. What this study adds This study explored the potential function of MAOA in drug-resistant NSCLC and might consider MAOA as a promising target for the treatment of drug-resistant NSCLC.