Inflammation-associated signal pathways activation during drug resistance development in cancer cells
https://doi.org/10.29413/ABS.2025-10.3.5
Abstract
Background. Cancer drug resistance represents an obvious problem in clinical oncology. Among various intracellular pathways activated during drug resistance development, proinflammatory cascades considered to be involved as well. The inflammatory process may also play a key role in the formation of melanoma resistance to the chemotherapeutic agent dacarbazine.
The aim. To characterize differentially expressed genes and signaling pathways associated with cancer resistance to alkylating agent dacarbazine in melanoma cells in vivo with the use of high-throughput sequencing for transcriptomic profiling.
Methods. The effect of dacarbazine on melanoma cell gene expression was studied in a C57Bl6/B16 melanoma model in vivo. Mice were injected intraperitoneally with dacarbazine (50 mg/kg) on days 8, 10, and 12 after melanoma tumor transplantation. Total RNA was extracted from tumor nodes on the 14th day after melanoma transplantation to animals and the transcriptome was analyzed using a next generation sequencing method. Bioinformatic analysis was applied to identify differentially expressed genes and corresponding signal pathways.
Results. Twenty one differentially expressed genes were identified, of which an increase in expression was observed in 10 genes, and a decrease in expression activity was observed in 11 genes involved in signaling pathways associated with the inflammatory process “Comprehensive IL-17A signaling”, “Oxidative stress and redox pathway”, “TNF alpha NF-kB signaling pathway”.
Conclusions. Dacarbazine alters the expression of genes regulating inflammation, which may play a role in the development of chemoresistance.
About the Authors
E. Z. Lapkina
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University
Russian Federation
Russian Federation
Ekaterina Z. Lapkina – Cand. Sc. (Biol.), associate Professor Pathophysiology Department
P. Zeleznyak str., 1, Krasnoyarsk 660022
I. S. Zinchenko
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University
Russian Federation
Russian Federation
Ivan S. Zinchenko – assistant of the Pathophysiology department
P. Zeleznyak str., 1, Krasnoyarsk 660022
Е. I. Bondar
Siberian Federal University;
Krasnoyarsk Science Center of the Siberian Branch of the Russian Academy of Sciences
Russian Federation
Russian Federation
Evgeniya I. Bondar – Cand. Sc. (Biol.), senior researcher at the Laboratory of Genomic Research and Biotechnology; senior lecturer at the Department of genomics and bioinformatics
Svobodny Ave., 79, Krasnoyarsk 660041;
Akademgorodok Str., 50, Krasnoyarsk 660036
E. Yu. Sergeeva
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University
Russian Federation
Russian Federation
Ekaterina Yu. Sergeeva – Dr. Sc. (Med.), Professor, Professor of the Pathophysiology department
P. Zeleznyak str., 1, Krasnoyarsk 660022
T. G. Ruksha
Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University
Russian Federation
Russian Federation
Tatiana G. Ruksha – Dr. Sc. (Med.), Professor, Head of the Pathophysiology Department
P. Zeleznyak str., 1, Krasnoyarsk 660022
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Review
For citations:
Lapkina E.Z., Zinchenko I.S., Bondar Е.I., Sergeeva E.Yu., Ruksha T.G. Inflammation-associated signal pathways activation during drug resistance development in cancer cells. Acta Biomedica Scientifica. 2025;10(3):49-58. (In Russ.) https://doi.org/10.29413/ABS.2025-10.3.5
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