ArticlePloS one2012
Low molecular weight heparin ablates lung cancer cisplatin-resistance by inducing proteasome-mediated ABCG2 protein degradation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Towards an emerging role for anticoagulants in cancer therapy: a systematic review and meta-analysis.Frontiers in oral health · 2024Pooled it
- Randomised phase II trial of gemcitabine and nab-paclitaxel with necuparanib or placebo in untreated metastatic pancreas ductal adenocarcinoma.European journal of cancer (Oxford, England : 1990) · 2020Trial
- Enoxaparin induces apoptosis and autophagy, modulates inflammatory signaling, and reduces oxidative DNA damage in breast and liver cancer cells.Scientific reports · 2026Article
- Exploring the effects of tinzaparin and cisplatin on lung cancer cells in vitro.Cancer cell international · 2026Article
- Free-floating patient-derived organotypic tumor spheroids (PDOTS) from non-small cell lung cancer (NSCLC) tumors: a versatile tool for personalized testing of chemotherapeutic drugs.Research in pharmaceutical sciences · 2025Article
- Selenium Yeast and Fish Oil Combination Diminishes Cancer Stem Cell Traits and Reverses Cisplatin Resistance in A549 Sphere Cells.Nutrients · 2022Article
- Multidrug efflux transporter ABCG2: expression and regulation.Cellular and molecular life sciences : CMLS · 2021Review
- Anti-Tumor Effects of Biomimetic Sulfated Glycosaminoglycans on Lung Adenocarcinoma Cells in 2D and 3D In Vitro Models.Molecules (Basel, Switzerland) · 2020Article
- Article
- Six2 promotes non-small cell lung cancer cell stemness via transcriptionally and epigenetically regulating E-cadherin.Cell proliferation · 2019Article
- [Research Progress in the Therapeutic Strategy Based on Targeting at Lung Cancer Stem Cell].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2018Review
- Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Article
- ABC Transporters in Cancer Stem Cells: Beyond Chemoresistance.International journal of molecular sciences · 2017Review
- The Impact of the Low Molecular Weight Heparin Tinzaparin on the Sensitization of Cisplatin-Resistant Ovarian Cancers-Preclinical In Vivo Evaluation in Xenograft Tumor Models.Molecules (Basel, Switzerland) · 2017Article
- Low molecular weight heparin and cancer survival: clinical trials and experimental mechanisms.Journal of cancer research and clinical oncology · 2016Review
- ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer.Journal of biosciences · 2016Review
- The effect of therapeutic anticoagulation on overall survival in men receiving first-line docetaxel chemotherapy for metastatic castration-resistant prostate cancer.Clinical genitourinary cancer · 2015Article
- A cisplatin-resistant head and neck cancer cell line with cytoplasmic p53(mut) exhibits ATP-binding cassette transporter upregulation and high glutathione levels.Journal of cancer research and clinical oncology · 2014Article
- Interleukin 6 augments lung cancer chemotherapeutic resistance via ataxia-telangiectasia mutated/NF-kappaB pathway activation.Cancer science · 2014Article
- Intratumoral injection of cisplatin in various concentrations of ethanol for cisplatin-resistant lung tumors.Molecular and clinical oncology · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer side population (SP) cells, which are often referred to as cancer stem cells, are thought to be responsible for lung cancer chemotherapy resistance, and currently no drug can specifically target these cells. We hypothesize low-molecular-weight heparin (LMWH) may affect the biological properties of SP cells and could be used to clinically target these cells. To test this, SP cells were isolated from cisplatin (DDP)-resistant lung adenocarcinoma A549/DDP cells by flow cytometric sorting. Compared to non-SP cells, SP cells formed increased numbers of colonies in vitro, and had a 1000-fold increase in tumorigenicity in vivo. Proliferation and apoptosis assays demonstrated LMWH had no significant effect on lung SP cell proliferation or apoptosis. However, LMWH reduced lung SP cell colony formation ability and protein expression of the multidrug transporter, ABCG2, by FACS and western blot analyses without affecting its mRNA levels by RT-PCR. Consistently, immunohistochemistry stainings of ABCG2 in LMWH-treated tumor tissues were significantly reduced compared with those in controls. Further, we found proteasomal inhibitor MG132, but not lysosomal inhibitors leupeptin and pepstatin A, could restore ABCG2 protein levels in LMWH-treated SP cells. These suggest LMWH ablates lung SP cell chemoresistance by proteasome-mediated reduction of ABCG2 protein levels without affecting its mRNA levels. We also determined LMWH combined with cisplatin could overcome cisplatin-resistance and induced lung SP cells apoptosis both in vitro and in vivo. This study provides an experimental basis for using a combination of LMWH, which targets lung SP cells, with chemotherapy to improve lung cancer survival.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.