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Simultaneous use of erythropoietin and LFM‐A13 as a new therapeutic approach for colorectal cancer

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Titel: Simultaneous use of erythropoietin and LFM‐A13 as a new therapeutic approach for colorectal cancer
Autoren: Anna Tankiewicz‐Kwedlo, Justyna Magdalena Hermanowicz, Tomasz Domaniewski, Krystyna Pawlak, Małgorzata Rusak, Anna Pryczynicz, Arkadiusz Surazynski, Tomasz Kaminski, Adam Kazberuk, Dariusz Pawlak
Quelle: Br J Pharmacol
Verlagsinformationen: Wiley, 2018.
Publikationsjahr: 2018
Schlagwörter: 0301 basic medicine, Cell Count, Cell Cycle Proteins, Erythropoietin - therapeutic use, Agammaglobulinaemia tyrosine kinase - metabolism, Amides - pharmacology, erythropoietin - metabolism, Mice, Erythropoietin - pharmacology, Receptors, Antineoplastic Combined Chemotherapy Protocols, Agammaglobulinaemia Tyrosine Kinase, Receptors, Erythropoietin, Cell survival - drug effects, Amides - therapeutic use, 0303 health sciences, Nitriles - therapeutic use, Antineoplastic combined chemotherapy protocols - pharmacology, Drug Synergism, Cell cycle proteins, Cell count, Research Papers, Nitriles - adverse effects, 3. Good health, Colonic Neoplasms, Proto-oncogene proteins, Colorectal Neoplasms, Colonic neoplasms - drug therapy, Xenograft model antitumor assays, tumor, Protein-serine-threonine kinases, Cell Survival, Protein Serine-Threonine Kinases, Erythropoietin - adverse effects, 03 medical and health sciences, Cell Line, Tumor, Proto-Oncogene Proteins, Nitriles, Animals, Humans, Amides - adverse effects, Erythropoietin, Proto-oncogene proteins c-akt - metabolism, Colorectal neoplasms - drug therapy, Amides, Xenograft Model Antitumor Assays, Antineoplastic combined chemotherapy protocols - therapeutic use, Nitriles - pharmacology, Drug synergism, Cell line, Proto-Oncogene Proteins c-akt
Beschreibung: Background and PurposeBruton's tyrosine kinase (Btk) is a non‐receptor tyrosine kinase involved in the activation of signalling pathways responsible for cell maturation and viability. Btk has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anaemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin β (Epo) and LFM‐A13 (Btk inhibitor) on colon cancer in in vitro and in vivo models.Experimental ApproachDLD‐1 and HT‐29 human colon adenocarcinoma cells were cultured with Epo and LFM‐A13. Cell number and viability, and mRNA and protein levels of Epo receptors, Btk and Akt were assessed. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM‐A13.Key ResultsThe combination of Epo and LFM‐A13 mostly exerted a synergistic inhibitory effect on colon cancer cell growth. The therapeutic scheme used effectively killed the cancer cells and attenuated the Btk signalling pathways. Epo + LFM‐A13 also prevented the normal process of microtubule assembly during mitosis by down‐regulating the expression of Polo‐like kinase 1. The combination of Epo and LFM‐A13 significantly reduced the growth rate of tumour cells, while it showed high safety profile, inducing no nephrotoxicity, hepatotoxicity or changes in the haematological parameters.Conclusion and ImplicationsEpo significantly enhances the antitumour activity of LFM‐A13, indicating that a combination of Epo and LFM‐A13 has potential as an effective therapeutic approach for patients with colorectal cancer.
Publikationsart: Article
Other literature type
Sprache: English
ISSN: 1476-5381
0007-1188
DOI: 10.1111/bph.14099
Zugangs-URL: https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bph.14099
https://pubmed.ncbi.nlm.nih.gov/29160911
https://europepmc.org/article/MED/29160911
https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/bph.14099
https://onlinelibrary.wiley.com/doi/abs/10.1111/bph.14099
https://khepri-node.dev.meta-infra.org/papers/simultaneous-use-of-erythropoietin-and-lfm-a13-as/29160911
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14099
http://onlinelibrary.wiley.com/doi/10.1111/bph.14099/abstract
https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.14099
https://doi.org/10.1111/bph.14099
Rights: CC BY NC
Dokumentencode: edsair.doi.dedup.....466dacccd3da98e4aee5a38ccf466359
Datenbank: OpenAIRE
Beschreibung
Abstract:Background and PurposeBruton's tyrosine kinase (Btk) is a non‐receptor tyrosine kinase involved in the activation of signalling pathways responsible for cell maturation and viability. Btk has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anaemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin β (Epo) and LFM‐A13 (Btk inhibitor) on colon cancer in in vitro and in vivo models.Experimental ApproachDLD‐1 and HT‐29 human colon adenocarcinoma cells were cultured with Epo and LFM‐A13. Cell number and viability, and mRNA and protein levels of Epo receptors, Btk and Akt were assessed. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM‐A13.Key ResultsThe combination of Epo and LFM‐A13 mostly exerted a synergistic inhibitory effect on colon cancer cell growth. The therapeutic scheme used effectively killed the cancer cells and attenuated the Btk signalling pathways. Epo + LFM‐A13 also prevented the normal process of microtubule assembly during mitosis by down‐regulating the expression of Polo‐like kinase 1. The combination of Epo and LFM‐A13 significantly reduced the growth rate of tumour cells, while it showed high safety profile, inducing no nephrotoxicity, hepatotoxicity or changes in the haematological parameters.Conclusion and ImplicationsEpo significantly enhances the antitumour activity of LFM‐A13, indicating that a combination of Epo and LFM‐A13 has potential as an effective therapeutic approach for patients with colorectal cancer.
ISSN:14765381
00071188
DOI:10.1111/bph.14099