0
Lung Cancer |

Down-regulated SIRT1 by Nonsteroidal Antiinflammatory Drugs Is to Inhibit TGF-1-Induced Epithelial-Mesenchymal Transition and to Suppress Migration and Invasion in Lung Cancer FREE TO VIEW

Ki Eun Hwang, MD; Kyung-Hwa Cho, MD; Eun-Taik Jeong, MD; Hak-Ryul Kim, MD
Author and Funding Information

Wonkwang University Hospital, Iksan City, Korea (the Republic of)


Chest. 2015;148(4_MeetingAbstracts):548A. doi:10.1378/chest.2280444
Text Size: A A A
Published online

Abstract

SESSION TITLE: Lung Cancer Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM

PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to suppress lung cancer invasion and metastasis. However, the mechanism in lung cancer epithelial-mesenchymal transition (EMT) by NSAIDs is not clearly known. The class III deacetylase sirtuin 1 (SIRT1) possesses both pro- and anticarcinogenic properties. In this study, we investigated the role of NSAIDs as an inhibitor of TGF-b1-induced EMT, and the underlying mechanisms of suppressing lung cancer migration and invasion by celexiband sulindac.

METHODS: We evaluated the efficacy of celecoxib and sulindac in TGF-b1-induced EMT. EMT-related molecular alterations were detected by western blotting. Electric cell-substrate impedance sensing (ECIS) was used to evaluate the migration and invasion of A549 cells. The matrix metalloproteinase (MMP) gelatinolytic activity was determined by gelatin zymography analysis, and protein expression was measured by western blotting. In addition,SIRT1 was knocked down or overexpressed to determine its role in preventing TGF-b1-induced EMT by celecoxib or sulindac.

RESULTS: Celecoxib was more effective in preventing TGF-b1-induced EMT, as compared with sulindac treatment, indicating upregulation of the epithelial marker, E-cadherin, and downregulation of N-cadherin, mesenchymal and transcription factors. Moreover, ECIS assay showed that celecoxib and sulindac could inhibit TGF-b1-enhanced migration and invasion of A549 cells. Increment in MMP-9 expression compared to that of MMP-2 following activation of TGF-b1 was also observed. However, treatment with celecoxib or sulindac inhibited MMP-9 expression. SIRT1 downregulation enhanced reverse of TGF-b1-induced EMT by celecoxib or sulindac. In contrast, SIRT1 upregulation had a relevant role in TGF-b1-induced EMT.

CONCLUSIONS: Celecoxib and sulindac can inhibit TGF-b1-induced EMT and suppress lung cancer migration and invasion via down-regulation of SIRT-1. SIRT1 is positive regulator of TGF-b1-induced EMT and potential therapeutic target to reverse EMT and to prevent lung cancer progression.

CLINICAL IMPLICATIONS: :Celecoxib and sulindac can inhibit TGF-b1-induced EMT and suppress lung cancer migration and invasion via down-regulation of SIRT-1. SIRT1 is positive regulator of TGF-b1-induced EMT and potential therapeutic target to reverse EMT and to prevent lung cancer progression.

DISCLOSURE: The following authors have nothing to disclose: Ki Eun Hwang, Kyung-Hwa Cho, Eun-Taik Jeong, Hak-Ryul Kim

No Product/Research Disclosure Information


Figures

Tables

References

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543