NAD(P)H quinone oxidoreductase-1 expression promotes self-renewal and therapeutic resistance in non-small cell lung cancer Journal Article
| Authors: | Madajewski, B.; Boatman, M. A.; Martinez, I.; Carter, J. H.; Bey, E. A. |
| Article Title: | NAD(P)H quinone oxidoreductase-1 expression promotes self-renewal and therapeutic resistance in non-small cell lung cancer |
| 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. © 2023 by the authors. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; genetics; cisplatin; protein function; cell proliferation; metabolism; protein depletion; carcinoma, non-small-cell lung; lung neoplasms; antineoplastic activity; in vitro study; drug resistance; pathology; drug resistance, neoplasm; lung tumor; cancer stem cell; quinone derivative; quinones; therapy resistance; proliferation; oxidoreductase; self-renewal; non-small cell lung cancer; nad; nicotinamide adenine dinucleotide; non small cell lung cancer; tumor-initiating cells; cell self-renewal; spheroids; reduced nicotinamide adenine dinucleotide (phosphate) dehydrogenase (quinone); nad(p)h dehydrogenase (quinone); nadh, nadph oxidoreductases; tumor spheroid; gene knockdown; humans; human; article; nqo1; a-549 cell line; chemo-resistance; nad(p)h quinone oxidoreductase 1 |
| Journal Title: | Genes |
| Volume: | 14 |
| Issue: | 3 |
| ISSN: | 2073-4425 |
| Publisher: | MDPI |
| Date Published: | 2023-03-01 |
| Start Page: | 607 |
| Language: | English |
| DOI: | 10.3390/genes14030607 |
| PUBMED: | 36980879 |
| PROVIDER: | scopus |
| PMCID: | PMC10047941 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2023 -- Source: Scopus |
