ArticleCellular and molecular life sciences : CMLS2022
HIF-1-dependent heme synthesis promotes gemcitabine resistance in human non-small cell lung cancers via enhanced ABCB6 expression.
Article in Cellular and molecular life sciences : CMLS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy.Nature cancer · 2026Article
- TargetingZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Article
- A mitochondrial-related gene signature predicts prognosis and immunotherapy response in hepatocellular carcinoma.Scientific reports · 2025Article
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- Unraveling the triad of hypoxia, cancer cell stemness, and drug resistance.Journal of hematology & oncology · 2025Review
- Article
- Hypoxia inducible factor-1α promotes non-small cell lung cancer progression by activating leptin receptor transcription.Cancer biomarkers : section A of Disease markers · 2025Article
- The role of mitochondrial dysfunction in the cytotoxic synergistic effect of gemcitabine and arsenic on breast cancer.PloS one · 2025Article
- KRAS G12C inhibition enhances efficacy to conventional chemotherapy in KRAS-mutant NSCLC.Frontiers in oncology · 2025Article
- LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.International journal of biological sciences · 2024Review
- Review
- Nanomedicines for Overcoming Cancer Drug Resistance.Pharmaceutics · 2022Review
- KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma.Frontiers in pharmacology · 2022Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Gemcitabine is commonly used to treat various cancer types, including human non-small cell lung cancer (NSCLC). However, even cases that initially respond rapidly commonly develop acquired resistance, limiting our ability to effectively treat advanced NSCLC. To gain insight for developing a strategy to overcome gemcitabine resistance, the present study investigated the mechanism of gemcitabine resistance in NSCLC according to the involvement of ATP-binding cassette subfamily B member 6 (ABCB6) and heme biosynthesis. First, an analysis of ABCB6 expression in human NSCLCs was found to be associated with poor prognosis and gemcitabine resistance in a hypoxia-inducible factor (HIF)-1-dependent manner. Further experiments showed that activation of HIF-1α/ABCB6 signaling led to intracellular heme metabolic reprogramming and a corresponding increase in heme biosynthesis to enhance the activation and accumulation of catalase. Increased catalase levels diminished the effective levels of reactive oxygen species, thereby promoting gemcitabine-based resistance. In a mouse NSCLC model, inhibition of HIF-1α or ABCB6, in combination with gemcitabine, strongly restrained tumor proliferation, increased tumor cell apoptosis, and prolonged animal survival. These results suggest that, in combination with gemcitabine-based chemotherapy, targeting HIF-1α/ABCB6 signaling could result in enhanced tumor chemosensitivity and, thus, may improve outcomes in NSCLC patients.
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