ArticleTranslational oncology2009
Combination of enzastaurin and pemetrexed inhibits cell growth and induces apoptosis of chemoresistant ovarian cancer cells regulating extracellular signal-regulated kinase 1/2 phosphorylation.
Article in Translational oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- Review
- ADAM17 Inhibition Increases the Impact of Cisplatin Treatment in Ovarian Cancer Spheroids.Cancers · 2021Article
- Fatty acid synthase overexpression: target for therapy and reversal of chemoresistance in ovarian cancer.Journal of translational medicine · 2015Article
- Combinatorial inhibition of Plk1 and PKCβ in cancer cells with different p53 status.Oncotarget · 2014Article
- Prolonged mechanical ventilation alters the expression pattern of angio-neogenetic factors in a pre-clinical rat model.PloS one · 2013Article
- The protein kinase C inhibitor enzastaurin exhibits antitumor activity against uveal melanoma.PloS one · 2012Article
- Combined treatment with TRAIL and PPARγ ligands overcomes chemoresistance of ovarian cancer cell lines.Journal of cancer research and clinical oncology · 2011Article
- Changes in gene expression and cellular architecture in an ovarian cancer progression model.PloS one · 2011Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
New strategies in the therapy for malignant diseases depend on a targeted influence on signal transduction pathways that regulate proliferation, cell growth, differentiation, and apoptosis by the activation of serine/threonine kinases. Enzastaurin (LY317615.HCl), a selective inhibitor of protein kinase Cbeta (PKCbeta), is one of these new drugs and causes inhibition of proliferation and induction of apoptosis. Pemetrexed, a multitarget inhibitor of folate pathways, is broadly active in a wide variety of solid tumors. Therefore, the effect of enzastaurin and the combination treatment with pemetrexed was analyzed when applied to the drug-sensitive ovarian cancer cell line HEY and various subclones with drug resistance against cisplatin, etoposide, docetaxel, and paclitaxel, as well as pemetrexed, and gemcitabine. In these novel chemoresistant subclones, the expression of the enzastaurin targets PKCbetaII and glycogen synthase kinase 3beta (GSK3beta) was analyzed. Exposition to enzastaurin showed various inhibitory effects on phosphorylated forms of GSK3beta and the mitogen-activated protein kinase extracellular signal-regulated kinase 1/2. Cell proliferation experiments identified the cell line-specific half-maximal inhibitory concentration values of enzastaurin and a synergistic inhibitory effect by cotreatment with the antifolate pemetrexed. Induction of apoptosis by enzastaurin treatment was investigated by Cell Death Detection ELISA and immunoblot analyses. Simultaneous treatment with pemetrexed resulted in an enhanced inhibition of proliferation and induction of apoptosis even in partial enzastaurin-resistant cells. Therefore, the combinational effect of enzastaurin and pemetrexed can have promise in clinical application to overcome the fast-growing development of resistance to chemotherapy in ovarian cancer.
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Registered trials
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