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NAD(P)H Quinone Oxidoreductase-1 Expression Promotes Self-Renewal and Therapeutic Resistance in Non-Small Cell Lung Cancer.
| Content Provider | Europe PMC |
|---|---|
| Author | Madajewski, Brian Boatman, Michael A. Martinez, Ivan Carter, Julia H. Bey, Erik A. |
| Editor | Goto, Taichiro |
| Copyright Year | 2023 |
| Abstract | Identifying cellular drivers responsible for enhancing cancer cell resistance to therapeutics provides critical information for designing more effective drugs. Populations of slowly growing, self-renewing, chemo-resistant cells purportedly contribute to the development of therapeutic resistance in many solid tumors. In the current study, we implemented a tumor spheroid model to determine whether NAD(P)H quinone oxidoreductase-1 (NQO1) was requisite for self-renewal and promotion of the drug-resistant phenotype in non-small cell lung cancer (NSCLC). We found that stable depletion of NQO1 in A549 and H358 human NSCLC tumor models inhibits self-renewal capabilities, as demonstrated by a reduced ability to form primary, secondary, and tertiary spheroids. In contrast, the rescue of NQO1 expression restored the tumor cells’ ability to form spheroids. Additionally, we discovered that NQO1 depletion renders cisplatin-refractory tumor spheroids highly susceptible to drug treatment. Together, these results suggest that NQO1 loss reduces the self-renewing capabilities of NSCLC cells and enhances their susceptibility to clinically relevant therapeutics. These findings describe a novel role for NQO1 and suggest that combining NQO1-inhibitors with conventional chemotherapeutics may enhance anti-tumor effects. |
| Journal | Genes (Basel) |
| Volume Number | 14 |
| PubMed Central reference number | PMC10047941 |
| Issue Number | 3 |
| PubMed reference number | 36980879 |
| e-ISSN | 20734425 |
| DOI | 10.3390/genes14030607 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2023-02-28 |
| Access Restriction | Open |
| Rights License | Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors. |
| Subject Keyword | NQO1 self-renewal tumor-initiating cells chemo-resistance non-small cell lung cancer proliferation spheroids |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Genetics (clinical) |
