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The intensification of anticancer activity of LFM-A13 by erythropoietin as a possible option for inhibition of breast cancer.
Journal of Enzyme inhibition and Medicinal Chemistry ( IF 5.6 ) Pub Date : 2020-09-10 , DOI: 10.1080/14756366.2020.1818738
Dariusz Rozkiewicz 1 , Justyna Magdalena Hermanowicz 1, 2 , Anna Tankiewicz-Kwedlo 3 , Beata Sieklucka 1 , Krystyna Pawlak 3 , Robert Czarnomysy 4 , Krzysztof Bielawski 4 , Arkadiusz Surazynski 5 , Joanna Kalafut 6 , Alicja Przybyszewska 6 , Mariusz Koda 7 , Katarzyna Jakubowska 8 , Adolfo Rivero-Muller 6 , Dariusz Pawlak 1
Affiliation  

Recombinant human erythropoietin (Epo) is an effective and convenient treatment for cancer-related anaemia. In our study for the first time, we evaluated the effect of simultaneous use of Epo and Bruton’s tyrosine kinase (BTK) inhibitor LFM-A13 on the viability and tumour development of breast cancer cells. The results demonstrated that Epo significantly intensifies the anticancer activity of LFM-A13 in MCF-7 and MDA-MB-231. The featured therapeutic scheme efficiently blocked the tumour development in zebrafish experimental cancer model. Epo and LFM-A13 administered together resulted in effective cell killing, accompanied by attenuation of the BTK signalling pathways, loss of mitochondrial membrane potential (MMP), accumulation of apoptotic breast cancer cells with externalised PS, a slight increase in phase G0/G1 and a reduction in cyclin D1 expression. Simultaneous use of Epo with LFM-A13 inhibited early stages of tumour progression. This therapeutic scheme may be rationale for further possible research.



中文翻译:

促红细胞生成素增强LFM-A13的抗癌活性可能是抑制乳腺癌的一种可能选择。

重组人促红细胞生成素(Epo)是一种用于癌症相关性贫血的有效便捷的治疗方法。在我们的首次研究中,我们评估了同时使用Epo和Bruton酪氨酸激酶(BTK)抑制剂LFM-A13对乳腺癌细胞的生存能力和肿瘤发展的影响。结果表明,Epo显着增强了LFM-A13在MCF-7和MDA-MB-231中的抗癌活性。特色治疗方案有效地阻止了斑马鱼实验癌症模型中的肿瘤发展。一起使用Epo和LFM-A13可导致有效的细胞杀伤,并伴随BTK信号传导途径的减弱,线粒体膜电位(MMP)的丧失,外在PS导致的凋亡性乳腺癌细胞的蓄积,G0 / G1期略有增加,而cyclin D1表达降低。Epo与LFM-A13同时使用可抑制肿瘤进展的早期阶段。该治疗方案可能是进一步可能研究的理由。

更新日期:2020-09-11
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