ArticleJournal of cancer research and clinical oncology2005
Effect of the cyclin-dependent kinases inhibitor p27 on resistance of ovarian cancer multicellular spheroids to anticancer chemotherapy.
Article in Journal of cancer research and clinical oncology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 38 citations in OpenAlex.
- 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
- PDK4 promotes tumorigenesis and cisplatin resistance in lung adenocarcinoma via transcriptional regulation of EPAS1.Cancer chemotherapy and pharmacology · 2021Article
- Exploring the Potential of Drug Response Assays for Precision Medicine in Ovarian Cancer.International journal of molecular sciences · 2020Review
- Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation.Experimental hematology & oncology · 2020Article
- Reversing platinum resistance in ovarian cancer multicellular spheroids by targeting Bcl-2.OncoTargets and therapy · 2019Article
- Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model.Journal of theoretical biology · 2017Article
- Modeling the Dynamics of High-Grade Serous Ovarian Cancer Progression for Transvaginal Ultrasound-Based Screening and Early Detection.PloS one · 2016Article
- Beclin-1 expression is retained in high-grade serous ovarian cancer yet is not essential for autophagy induction in vitro.Journal of ovarian research · 2015Article
- Combination of AKT inhibition with autophagy blockade effectively reduces ascites-derived ovarian cancer cell viability.Carcinogenesis · 2014Article
- miR-222 is upregulated in epithelial ovarian cancer and promotes cell proliferation by downregulating P27Oncology letters · 2013Article
- Low expression of the X-linked ribosomal protein S4 in human serous epithelial ovarian cancer is associated with a poor prognosis.BMC cancer · 2013Article
- Cell-cell and cell-matrix dynamics in intraperitoneal cancer metastasis.Cancer metastasis reviews · 2012Review
- Multicellular tumor spheroid formation in duplex microcapsules for analysis of chemosensitivity.Cancer science · 2012Article
- An integrative approach to identify YB-1-interacting proteins required for cisplatin resistance in MCF7 and MDA-MB-231 breast cancer cells.Cancer science · 2011Article
- Identification of p27/KIP1 expression level as a candidate biomarker of response to rapalogs therapy in human cancer.Journal of molecular medicine (Berlin, Germany) · 2010Article
- Three-dimensional neuroblastoma cell culture: proteomic analysis between monolayer and multicellular tumor spheroids.Pediatric surgery international · 2008Article
- Global gene expression analysis of early response to chemotherapy treatment in ovarian cancer spheroids.BMC genomics · 2008Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeA low proliferating fraction in solid tumors limits the effectiveness of cell-cycle-dependent chemotherapeutic agents. To understand the molecular basis of such resistance, we examined the expression of the cyclin-dependent kinases inhibitor p27, and relationship with drug resistance and P-gp expression in ovarian cancer multicellular spheroids.
methodsWe cultured ovarian cancer cells (A2780 and CAOV3) as multicellular spheroids and examined the expression of p27 and P-glycoprotein (P-gp) by western blot, flow cytometry and confocal. We also analyzed the cell-cycle distribution by flow cytometry. In addition, trypan blue exclusion testing and cell apoptosis analysis were used to detect the sensitivity to Taxol.
resultsWhen transferred from monolayer to three-dimensional culture, a consistent upregulation of p27 protein and P-gp protein was observed in ovarian cancer cell lines. Compared with monolayer cells, there was a significant increase of G0-G1 phase cells and decrease of S and G2-M phase cells in spheroid cells. Aggregates of cells showed higher cell viability than monolayer cells. Antisense oligodeoxynucleotide (ASON) -mediated downregulation of p27 reduced intercellular adhesion, increased cell proliferation, downregulated P-gp expression and sensitized cells to Taxol.
conclusionsOur results implicate that p27 serves as a regulator of drug resistance in ovarian tumors. ASON-mediated alteration of p27 reverses resistance of ovarian cancer to anticancer agents that are associated with increased sensitivity of ovarian cancer cells to chemotherapeutic agents.
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