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

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Abstract
Introduction. Human cytomegalovirus 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 fullerene dC60) represents a promising strategy. The potential to overcome human cytomegalovirus mediated chemoresistance opens new avenues for developing combined therapeutic approaches in oncology. Aim – to evaluate the impact of human cytomegalovirus infection on the resistance of hepatocellular carcinoma and promyelocytic leukemia cells to doxorubicin, 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, Real-Time Polymerase Chain Reaction, Quantitative Reverse Transcription Polymerase Chain Reaction and MTT assay. Results. Human cytomegalovirus infection reduced doxorubicin cytotoxicity by 30% in both hepatocellular carcinoma and promyelocytic leukemia cells. In monocytic leukemia cells, combined treatment with doxorubicin and dC60 restored chemosensitivity to human cytomegalovirus infected cells, achieving 93% tumor cell death at half the standard doxorubicin concentration. Conclusion. Human cytomegalovirus infection induces doxorubicin resistance in both hematopoietic (promyelocytic leukemia, monocytic leukemia) and solid (hepatocellular carcinoma) tumor models. Importantly, combined treatment doxorubicin with aqueous fullerene dC60 not only overcomes virus-mediated drug resistance in monocytic leukemia cells but also enhances cytotoxicity at reduced doxorubicin concentrations, offering prospects for developing less toxic combined therapeutic regimens.

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