International journal of molecular sciences · 2025
Transcriptomic and Cytogenetic Analysis of Oxaliplatin-Resistant Colorectal Adenocarcinoma HCT116 Cells to Identify Markers Associated with Platinum Resistance.
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Morshneva Alisa, Gnedina Olga, Fedotova Ksenia, Yartseva Natalija, Aksenov Nikolay, Igotti Maria
Аннотация
Platinum-based chemotherapy resistance remains a critical barrier in colorectal cancer (CRC) treatment. In this study, cytogenetic karyotyping was combined with transcriptomic profiling (RNA-seq) to elucidate resistance mechanisms by comparing two CRC cell lines: oxaliplatin-sensitive HCT116 and its resistant derivative HCT116 oxpl-R. Karyotyping unveiled tetraploidization and extensive genomic rearrangements in resistant cells, accompanied by prominent transcriptomic changes: 1807 differentially expressed genes (1216 upregulated and 519 downregulated). Pathway enrichment highlighted altered redox homeostasis and metabolic adaptation. Specifically, HCT116 oxpl-R cells exhibited elevated reactive oxygen species (ROS) production and enhanced energy metabolism. These findings establish a direct association between structural genomic alterations, transcriptional rewiring, and functional phenotypes in platinum resistance, providing a framework for targeting metabolic vulnerabilities in refractory CRC.