Resistance and сhemosensitivity restoration in human cytomegalovirus-infected tumor cells to doxorubicin through combined treatment with aqueous fullerene dC60

Introduction. Human cytomegalovirus (HCMV) infection can induce tumor cell resistance to chemotherapeutic agents through modulation of apoptotic pathways. In the search for alternative approaches to overcome virus-associated drug resistance, the application of nanomaterials (aqueous fulleren dC₆₀) represents a promising strategy. The potential to overcome HCMV-mediated chemoresistance opens new avenues for developing combined therapeutic approaches in oncology.

Aim – to evaluate the impact of HCMV infection on the resistance of hepatocellular carcinoma and promyelocytic leukemia cells to doxorubicin (DOX), as well as the potential of aqueous fullerene dC₆₀ to restore chemosensitivity in monocytic leukemia cells.

Materials and methods. Hepatocellular carcinoma cells (Huh 7.5), promyelocytic leukemia cells (HL-60), monocytic leukemia cells (THP-1), and HCMV AD169 were used. The experimental procedures included standard cell culture techniques, virological methods, immunocytochemistry, Western blotting, RT-PCR, qRT-PCR and MTT assay.

Results. HCMV infection reduced DOX cytotoxicity by 30% in both hepatocellular carcinoma and promyelocytic leukemia cells. In monocytic leukemia cells, combined treatment with DOX and dC₆₀ restored chemosensitivity to HCMV-infected cells, achieving 93% tumor cell death at half the standard DOX concentration.

Conclusion. HCMV infection induces DOX resistance in both hematopoietic (promyelocytic leukemia, monocytic leukemia) and solid (hepatocellular carcinoma) tumor models. Importantly, combined treatment DOX with aqueous fullerene dC₆₀ not only overcomes virus-mediated drug resistance in monocytic leukemia cells but also enhances cytotoxicity at reduced DOX concentrations, offering prospects for developing less toxic combined therapeutic regimens.