XMU-MP-1, the Hippo Signaling Pathway MST-1 Kinase Inhibitor, Prevents the Development of Drug Resistance to Doxorubicin in Hematological Tumor Cells

Background/Objectives: Search for the new drugs capable of suppressing the development of drug resistance in tumor cells is extremely important for clinical practice. Cell signaling pathway inhibitors that control cell proliferation and death can be used in the complex therapy of malignant tumors. Methods: Cell cycle assay by flow cytometry, In Vitro Cell Viability Assay Cells chemosensitivity was analyzed by direct cell counting after trypan blue staining using microscope. Results: In the present work, we have shown that the combined action of doxorubicin and XMU-MP-1, the inhibitor of the MST1/2 kinase in the Hippo signaling pathway, prevents the development of drug resistance in Namalwa cells and significantly slows it down in K562 cells. and restores the sensitivity of resistant K562 cells to doxorubicin. We have shown that the combined action of doxorubicin and XMU-MP-1, causes a significant decrease in cell division rate and leads to the death of hematological tumor cells the Burkitt's lymphoma Namalwa, and myeloma K562 cells compared to monotherapy. Cell cycle analysis has demonstrated that the combined action of XMU-MP-1 and doxorubicin results in a catastrophic disruption of the cell cycle, and a significant increase in the number of cells undergoing apoptosis containing fragmented DNA. Conclusions: Thus, XMU-MP-1 can potentially be used in combination with anthracy-clines for the treatment of hematological malignancies and, in particular, the drug-resistant forms of cancer.