Combined anticancer therapy with imidazoacridinone analogue C-1305 and paclitaxel in human lung and colon cancer xenografts-Modulation of tumour angiogenesis.

Autor: Świtalska M; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland., Filip-Psurska B; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland., Milczarek M; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland., Psurski M; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland., Moszyńska A; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdańsk, Poland.; Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland., Dąbrowska AM; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland., Gawrońska M; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland., Krzymiński K; Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland., Bagiński M; Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdańsk, Poland., Bartoszewski R; Department of Biology and Pharmaceutical Botany, Medical University of Gdansk, Gdańsk, Poland., Wietrzyk J; Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Wrocław, Poland.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2022 Jul; Vol. 26 (14), pp. 3950-3964. Date of Electronic Publication: 2022 Jun 14.
DOI: 10.1111/jcmm.17430
Abstrakt: The acridanone derivative 5-dimethylaminopropylamino-8-hydroxytriazoloacridinone (C-1305) has been described as a potent inhibitor of cancer cell growth. Its mechanism of action in in vitro conditions was attributed, among others, to its ability to bind and stabilize the microtubule network and subsequently exhibit its tumour-suppressive effects in synergy with paclitaxel (PTX). Therefore, the objective of the present study was to analyse the effects of the combined treatment of C-1305 and PTX in vivo. In addition, considering the results of previous genomic analyses, particular attention was given to the effects of this treatment on tumour angiogenesis. Treatment with C-1305 revealed antitumor effect in A549 lung cancer cells, and combined treatment with PTX showed tendency to anticancer activity in HCT116 colon cancer xenografts. It also improved tumour blood perfusion in both tumour models. The plasma level of CCL2 was increased and that of PDGF was decreased after combined treatment with C-1305 and PTX. The experimental results showed that the levels of FGF1, TGF-β and Ang-4 decreased, whereas the levels of ERK1/2 and Akt phosphorylation increased in HCT116 tumour tissue following combined treatment with both drugs. The results of in vitro capillary-like structure formation assay demonstrated the inhibiting effect of C-1305 on this process. Although previous in vitro and in vivo studies suggested a positive effect of C-1305 on cancer cells, combined treatment of HCT116 human colon and A549 lung cancer cells with both PTX and C-1305 in vivo showed that the antitumor activity was restricted and associated with the modulation of tumour angiogenesis.
(© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: