UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Targeting NF-κB-Mediated Inflammatory Pathways in Cisplatin-Resistant NSCLC

Ryan, S-L; Beard, S; Barr, MP; Umezawa, K; Heavey, S; Godwin, P; Gray, SG; ... Baird, A-M; + view all (2019) Targeting NF-κB-Mediated Inflammatory Pathways in Cisplatin-Resistant NSCLC. Lung Cancer 10.1016/j.lungcan.2019.07.006. (In press). Green open access

[img]
Preview
Text
Heavey_Targeting NF-κB-Mediated Inflammatory Pathways in Cisplatin-Resistant NSCLC_AAM.pdf - Accepted version

Download (961kB) | Preview

Abstract

OBJECTIVES: The majority of patients with non-small cell lung cancer (NSCLC) present with advanced stage disease, at which time chemotherapy is usually the most common treatment option. While somewhat effective, patients treated with platinum-based regimens will eventually develop resistance, with others presenting with intrinsic resistance. Multiple pathways have been implicated in chemo-resistance, however the critical underlying mechanisms have yet to be elucidated. The aim of this project was to determine the role of inflammatory mediators in cisplatin-resistance in NSCLC. MATERIALS AND METHODS: Inflammatory mediator, NF-κB, and its associated pathways were investigated in an isogenic model of cisplatin-resistant NSCLC using age-matched parental (PT) and corresponding cisplatin-resistant (CisR) sublines. Pathways were assessed using mass spectrometry, western blot analysis and qRT-PCR. The cisplatin sensitizing potential of an NF-κB small molecule inhibitor, DHMEQ, was also assessed by means of viability assays and western blot analysis. RESULTS: Proteomic analysis identified dysregulated NF-κB responsive targets in CisR cells when compared to PT cells, with increased NF-κB expression identified in four out of the five NSCLC sub-types examined (CisR versus PT). DHMEQ treatment resulted in reduced NF-κB expression in the presence of cisplatin, and re-sensitized CisR cells to the cytotoxic effects of the drug. CONCLUSION: This study identified NF-ĸB as a potential therapeutic target in cisplatin-resistant NSCLC. Furthermore, inhibition of NF-ĸB using DHMEQ re-sensitized chemo-resistant cells to cisplatin treatment.

Type: Article
Title: Targeting NF-κB-Mediated Inflammatory Pathways in Cisplatin-Resistant NSCLC
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.lungcan.2019.07.006
Publisher version: https://doi.org/10.1016/j.lungcan.2019.07.006
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Non-small cell lung cancer, chemotherapy, resistance, cisplatin, DHMEQ, NF-κB
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10078144
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item