ArticleBMC cancer2012
HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast.
Article in BMC cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed, 174 citations in OpenAlex.
- Quantifying single-cell responses to irradiation in 3D.Frontiers in bioengineering and biotechnology · 2026Article
- HIF1A, BRG1, and p300 interaction confers paclitaxel-induced drug resistance by enabling the overexpression ofMolecular therapy. Oncology · 2025Article
- Clinicopathological characteristics and prognostic factors of invasive micropapillary carcinoma of the breast.Discover oncology · 2025Article
- Insights on the differences between two‑ and three‑dimensional culture systems in tumor models (Review).International journal of molecular medicine · 2025Review
- Article
- ERRα and HIF-1α Cooperate to Enhance Breast Cancer Aggressiveness and Chemoresistance Under Hypoxic Conditions.Cancers · 2025Article
- Influences of aqua-(2-formylbenzoato) triphenyltin(IV) on regression of hypoxic solid tumor through mitochondrial mediated pathway by inhibiting Hif-1 alpha.Scientific reports · 2025Article
- Micropapillary structure: A natural tumor collective invasion model with enhanced stem-like properties.Cancer science · 2025Review
- Omega-3 fatty acids: molecular weapons against chemoresistance in breast cancer.Cellular & molecular biology letters · 2025Review
- Melittin inhibits proliferation, migration, and invasion in osteosarcoma cell lines using 2D and 3D models.The journal of venomous animals and toxins including tropical diseases · 2025Article
- 3D bioprinting for the construction of drug testing models-development strategies and regulatory concerns.Frontiers in bioengineering and biotechnology · 2025Review
- Research progress in tumor angiogenesis and drug resistance in breast cancer.Cancer biology & medicine · 2024Review
- Nanomaterial-related hemoglobin-based oxygen carriers, with emphasis on liposome and nano-capsules, for biomedical applications: current status and future perspectives.Journal of nanobiotechnology · 2024Review
- Three-Dimensional Cultivation a Valuable Tool for Modelling Canine Mammary Gland Tumour Behaviour In Vitro.Cells · 2024Review
- Harnessing adrenergic blockade in stress-promoted TNBCFrontiers in pharmacology · 2024Article
- Hypoxia-inducible factor in breast cancer: role and target for breast cancer treatment.Frontiers in immunology · 2024Review
- Knockout cancer by nano-delivered immunotherapy using perfusion-aided scaffold-based tumor-on-a-chip.Nanotheranostics · 2024Review
- Three-DimensionalInternational journal of biological sciences · 2024Review
- miRNAs as short non-coding RNAs in regulating doxorubicin resistance.Journal of cell communication and signaling · 2023Review
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
32 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInvasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters.
methodsHIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay.
resultsIn MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids.
conclusionsMCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance.
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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.