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Simultaneous Use of Erythropoietin and LFM-A13 as a New Therapeutic Approach for Colorectal Cancer

Simultaneous Use of Erythropoietin and LFM-A13 as a New Therapeutic Approach for Colorectal Cancer

Anna Tankiewicz-Kwedlo, Justyna Magdalena Hermanowicz, Tomasz Domaniewski, Krystyna Pawlak, Małgorzata Rusak, Anna Pryczynicz, Arkadiusz Surazynski, Tomasz Kaminski, Adam Kazberuk, Dariusz Pawlak

Br J Pharmacol. 2018 Mar;175(5):743-762.

PMID: 29160911

Abstract:

Background and purpose:
Bruton'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 approach:
DLD-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 results:
The 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 implications:
Epo 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP244240242	LFM-A13		244240-24-2	Price

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