Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

Liu, Fei; Hu, Liang; Ma, Yuefan; Huang, Bingyu; Xiu, Zihan; Zhang, Peihua; Zhou, Keyuan; Tang, Xudong

doi:10.3892/ol.2017.7683

Cited by 41 publications

(47 citation statements)

References 35 publications

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“…When the HIF-1 pathway is upregulated, vascular endothelial growth factor, epithelial-mesenchymal transition and membrane-type 4 matrix metalloproteinase are activated (27)(28)(29). In the present study, DMOG treatment alone for 48 h was able to promote the colony-forming and migrating ability of HCC827 cells (Figs.…”

Section: Discussionsupporting

confidence: 51%

Hypoxia‑inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib

Jin

Zhou

et al. 2019

Oncol Lett

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The majority of patients with non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations inevitably progress in stage despite an initial substantial and rapid response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Previous research indicates that hypoxia may be associated with resistance to EGFR-TKIs in EGFR mutation-positive NSCLC. Therefore, the present study regulated the activity of hypoxia-inducible factor-1 (HIF-1) signaling pathway to observe if it is able to alter the sensitivity of lung cancer cells to gefitinib. The present study selected 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) and dimethyloxalylglycine (DMOG) as a HIF-1 signaling pathway inhibitor and activator, respectively, on HCC827 cells. Cells were incubated with different treatments for different durations: A blank control, DMOG, gefitinib, or DMOG and gefitinib combined, for 36 and 48 h; and then a blank control, YC-1, gefitinib, or YC-1 and gefitinib combined, for 16 and 28 h. A western blot analysis assay was performed to evaluate the protein expression levels of HIF-1α and phosphorylated hepatocyte growth factor receptor (p-MET), an MTT assay was used to determine cell proliferation, a colony formation assay was used to investigate the colony-forming ability and a wound healing assay was used to test the cell migration ability. Additionally, Pearson's correlation analysis was used to evaluate the correlation between p-Met and HIF-1α expression levels. Finally, it was identified that gefitinib and DMOG combined notably improve the growth and cell migration ability of HCC827 cells, compared with gefitinib alone. When gefitinib and YC-1 were combined, the inhibiting effect on the growth and cell migration ability of HCC827 cells was substantially enhanced, compared with the control cells. Pearson's correlation analysis revealed that the p-Met expression level had a strong positive correlation with HIF-1α expression levels. Thus, it was concluded that the HIF-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib. The positive correlation between p-Met and HIF-1α expression levels may be the underlying mechanism of the HIF-1 signaling pathway influencing the sensitivity of HCC827 cells to gefitinib.

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Section: Discussionsupporting

confidence: 51%

Hypoxia‑inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib

Jin

Zhou

et al. 2019

Oncol Lett

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“…The report that MAOA promoted NSCLC progression by mediating EMT raised an intriguing question of whether MAOA could serve as a therapeutic target in NSCLC treatment. 15 In this study, we used a previously synthesized compound, G11, whose in vitro antitumor efficacy and MAOA inhibitory ability have been confirmed in human prostate cancer cells. Through cytotoxicity evaluation and MAOA activity assay, we found that MAOA activities were relatively higher in paclitaxel-resistant NSCLC cells than in parental cells.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] A recent research result indicated that nonsmall cell lung cancer (NSCLC) tissues exhibited upregulation of MAOA compared with surrounding normal lung tissues. 15 Furthermore, a close relationship has been observed between increased MAOA expression in NSCLC tissues and Slug, N-cadherin and TWIST expression, EMT and the development of clinicopathological features of NSCLC such as later stage and lymph node metastasis. These findings suggest that MAOA may promote NSCLC progression by inducing EMT.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Zhao

et al. 2020

Thoracic Cancer

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Background: High expression of monoamine oxidase A (MAOA) in nonsmall 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 drugresistant NSCLC.

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“…NSCLC tissue specimens were collected from 45 patients with NSCLC in Affiliated Hospital of Guangdong Medical University (Zhanjiang, Guangdong, China) from 2007 to 2010. Meanwhile, the matched non-tumor adjacent lung tissues (1 cm from NSCLC tissues) were obtained from the same patients 37 . The criteria that patients should be met were according to our previous study 37 .…”

Section: Methodsmentioning

confidence: 99%

“…Meanwhile, the matched non-tumor adjacent lung tissues (1 cm from NSCLC tissues) were obtained from the same patients 37 . The criteria that patients should be met were according to our previous study 37 . This study was received the ethic approval from the local committee of Affiliated Hospital of Guangdong Medical University, and all clinical studies were performed according to the principles defined by the Declaration of Helsinki 37 .…”

Section: Methodsmentioning

confidence: 99%

PI3K/Akt/HIF-1α signaling pathway mediates HPV-16 oncoprotein-induced expression of EMT-related transcription factors in non-small cell lung cancer cells

Liu¹,

Huang²,

Xiu³

et al. 2018

J. Cancer

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Background: Our previous studies have demonstrated that human papillomaviruse (HPV)-16 oncoproteins promoted epithelial-mesenchymal transition (EMT), leading to non-small cell lung cancer (NSCLC) progression, but the underlying molecular mechanisms still remain unclear. PI3K/Akt/HIF-1α signaling pathway has been reported to mediate hypoxia-induced EMT. In this study, we further explored the role of PI3K/Akt/HIF-1α signaling pathway in HPV-16 oncoprotein-induced EMT in NSCLC cells.Methods: A549 and NCI-H460 NSCLC cells were transiently transfected with pEGFP-HPV-16 E6 or E7 constructs. Western blotting and RT-qPCR were respectively performed to determine the protein and mRNA expression of EMT-related transcription factors. HPV-16 E6 or E7-transfected NSCLC cells were co-transfected with specific HIF-1α-siRNA or pretreated with different concentrations of LY294002, a specific PI3K inhibitor, followed by the analysis of expression of EMT-related transcription factors. The correlation between HIF-1α and EMT-related transcription factors in NSCLC tissues was analyzed by immunohistochemical staining and Spearman rank correlation coefficient.Results: HPV-16 E6 and E7 oncoproteins upregulated the expression of Slug and Twist1, the EMT-related transcription factors, at both protein and mRNA levels in A549 and NCI-H460 cells. The co-transfection with specific HIF-1α-siRNA, but not the non-specific (NS)-siRNA, significantly abrogated HPV-16 oncoprotein-induced upregulation of ZEB1, Snail1, Slug, and Twist1 at both protein and mRNA levels. Additionally, pretreatment with LY294002 obviously blocked HPV-16 E6- and E7-induced Snail1, Slug, and Twist1 protein expression in A549 and NCI-H460 cells. Further analysis of clinical specimens showed that HIF-1α protein was strongly expressed in NSCLC tissues, which was positively correlated with ZEB1, Snail1, Slug, and Twist1 protein expression.Conclusions: PI3K/Akt/HIF-1α may contribute to the progression of HPV-associated NSCLC via mediating the expression of EMT-related transcription factors in NSCLC cells.

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Increased expression of monoamine oxidase A is associated with epithelial to mesenchymal transition and clinicopathological features in non-small cell lung cancer

Cited by 41 publications

References 35 publications

Hypoxia‑inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib

Hypoxia‑inducible factor-1 signaling pathway influences the sensitivity of HCC827 cells to gefitinib

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

PI3K/Akt/HIF-1α signaling pathway mediates HPV-16 oncoprotein-induced expression of EMT-related transcription factors in non-small cell lung cancer cells

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