ArticleBMC cancer2011
Molecular targeting of prostate cancer cells by a triple drug combination down-regulates integrin driven adhesion processes, delays cell cycle progression and interferes with the cdk-cyclin axis.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 28 citations in OpenAlex.
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- Glioblastoma Stem Cell-Derived Exosomes Enhance Stemness and Tumorigenicity of Glioma Cells by Transferring Notch1 Protein.Cellular and molecular neurobiology · 2020Article
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
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- Enrichment and characterization of cancer stem-like cells in ultra-low concentration of serum and non-adhesive culture system.American journal of translational research · 2018Article
- GOLPH3 and YB-1 Are Novel Markers Correlating With Poor Prognosis in Prostate Cancer.World journal of oncology · 2015Article
- Intensified antineoplastic effect by combining an HDAC-inhibitor, an mTOR-inhibitor and low dosed interferon alpha in prostate cancer cells.Journal of cellular and molecular medicine · 2015Article
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- HDAC-inhibition counteracts everolimus resistance in renal cell carcinoma in vitro by diminishing cdk2 and cyclin A.Molecular cancer · 2014Article
- Enrichment and characterization of cancer stem‑like cells from a cervical cancer cell line.Molecular medicine reports · 2014Article
- Role of SMAD4 in the mechanism of valproic acid's inhibitory effect on prostate cancer cell invasiveness.International urology and nephrology · 2014Article
- Article
- Prediction of effective drug combinations by chemical interaction, protein interaction and target enrichment of KEGG pathways.BioMed research international · 2013Article
- RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis.Cancers · 2012Article
- Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer.Diagnostic pathology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSingle drug use has not achieved satisfactory results in the treatment of prostate cancer, despite application of increasingly widespread targeted therapeutics. In the present study, the combined impact of the mammalian target of rapamycin (mTOR)-inhibitor RAD001, the dual EGFr and VGEFr tyrosine kinase inhibitor AEE788 and the histone deacetylase (HDAC)-inhibitor valproic acid (VPA) on prostate cancer growth and adhesion in vitro was investigated.
methodsPC-3, DU-145 and LNCaP cells were treated with RAD001, AEE788 or VPA or with a RAD-AEE-VPA combination. Tumor cell growth, cell cycle progression and cell cycle regulating proteins were then investigated by MTT-assay, flow cytometry and western blotting, respectively. Furthermore, tumor cell adhesion to vascular endothelium or to immobilized extracellular matrix proteins as well as migratory properties of the cells was evaluated, and integrin α and β subtypes were analyzed. Finally, effects of drug treatment on cell signaling pathways were determined.
resultsAll drugs, separately applied, reduced tumor cell adhesion, migration and growth. A much stronger anti-cancer effect was evoked by the triple drug combination. Particularly, cdk1, 2 and 4 and cyclin B were reduced, whereas p27 was elevated. In addition, simultaneous application of RAD001, AEE788 and VPA altered the membranous, cytoplasmic and gene expression pattern of various integrin α and β subtypes, reduced integrin-linked kinase (ILK) and deactivated focal adhesion kinase (FAK). Signaling analysis revealed that EGFr and the downstream target Akt, as well as p70S6k was distinctly modified in the presence of the drug combination.
conclusionsSimultaneous targeting of several key proteins in prostate cancer cells provides an advantage over targeting a single pathway. Since strong anti-tumor properties became evident with respect to cell growth and adhesion dynamics, the triple drug combination might provide progress in the treatment of advanced prostate cancer.
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