ArticleOncoTargets and therapy2019
Reversing platinum resistance in ovarian cancer multicellular spheroids by targeting Bcl-2.
Article in OncoTargets and therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Drug resistance biomarkers in ovarian cancer: a bibliometric study from 2017 to 2022.Frontiers in oncology · 2024Pooled it
- Cystathionine beta-synthase promotes anoikis resistance and transcoelomic metastasis in ovarian cancer via SP1- ITGB1 regulation.Experimental hematology & oncology · 2026Article
- Chemoresistance in Ovarian Cancer and Association with Circadian Rhythm.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- The role of cytokines in ovarian cancer drug resistance.International journal of cancer · 2026Review
- A vascularized three-dimensional model integrating primary breast tumor cells and microvascular fragments: mimicking the tumor microenvironment involved in chemoresistance.Cancer cell international · 2026Article
- Omics Investigations of Prostate Cancer Cells Exposed to Simulated Microgravity Conditions.Biomolecules · 2025Article
- Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer.World journal of surgical oncology · 2024Article
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Toxicity and autophagy effects of fluorinated cycloplatinated(II) complex bearing dppm ligand on cancer cells inMolecular biology research communications · 2023Article
- Review
- Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components.International journal of molecular sciences · 2022Review
- Patient-Derived Ovarian Cancer Spheroids Rely on PI3K-AKT Signaling Addiction for Cancer Stemness and Chemoresistance.Cancers · 2022Article
- Review
- Small Molecule Targeting of Oxysterol-Binding Protein (OSBP)-Related Protein 4 and OSBP Inhibits Ovarian Cancer Cell Proliferation in Monolayer and Spheroid Cell Models.ACS pharmacology & translational science · 2021Article
- Theasaponin EMolecules (Basel, Switzerland) · 2021Article
- Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer.International journal of molecular sciences · 2020Review
- Identification of BCL-XL as highly active survival factor and promising therapeutic target in colorectal cancer.Cell death & disease · 2020Article
- Bcl‑2 family: Novel insight into individualized therapy for ovarian cancer (Review).International journal of molecular medicine · 2020Review
- Review
- Strategies for Delivery of siRNAs to Ovarian Cancer Cells.Pharmaceutics · 2019Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePeritoneal metastasis is the most common pathway for the spread of ovarian cancer. Ovarian cancer cells in ascites prefer to aggregate into the more chemoresistant multicellular spheroids (MCSs), leading to treatment failure and disease recurrence. We previously established a suspension MCS model of ovarian cancer cells in vitro and found that the MCS cells acquired drug resistance to cisplatin. In the present study, we aimed to uncover the underlying mechanism of the platinum resistance of MCS and the potential targets to reverse the drug resistance. MATERIALS AND
methodsMCS models were established for the phenotypic studies, including proliferation, invasion, migration, drug resistance, apoptosis assays, and signaling pathway analysis. The key molecule, Bcl-2, was screened by profile analysis and validated by Western blotting. siRNA was used to verify the anti-cisplatin-induced apoptosis effect of Bcl-2. The Bcl-2 inhibitor, ABT-737, was used for improving the sensitivity of MCS to cisplatin. The 50% inhibitory concentrations (IC50) were measured by viability assays treated with different concentrations of cisplatin. Flow cytometry and Western blotting were used for quantification of drug-induced apoptosis.
resultsThe ovarian cancer MCS showed a proliferation-stagnant but invasive phenotype when resuspended. When treated with cisplatin, MCS cells showed much higher viability, with significantly fewer apoptotic cells than the adherent cells. Levels of Bcl-2 were upregulated in ovarian cancer ascitic cells and MCS cells. Bcl-2 knockdown by siRNA or blockage by ABT-737 enhanced the cisplatin-induced apoptosis and reduced the 50% inhibitory concentrations of cisplatin for MCS by 58.5% and 88.2%, respectively.
conclusionThe upregulated Bcl-2 contributes to cisplatin resistance in our MCS model and targeting it sensitizes the MCS to cisplatin treatment. This provides us a preliminary treatment method for ovarian cancer peritoneal metastasis.
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