Resistance of THP-1 Leukemia Cells Infected with Cytomegalovirus to Anti-tumor Antibiotic Doxorubicin and Restoration of the Sensitivity by Inhibitors of the PI3K/AKT/mTOR Molecular Pathway

Chernoryzh, Ya. Yu.; Федорова, Н. Е.; Yurlov, K.I.; Simonov, Ruslan A.; Корнев, А. Б.; Карпов, Д. С.; Zakirova, Natalia F.; Ivanov, Alexander; Кущ, А А; Gintsburg, A. L.

doi:10.1134/s1607672919060073

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“…Given that autophagy intensifies in HMCV-infected THP-1 cells [ 153 ], it is possible to assume that autophagy is involved in the development of doxorubicin resistance in leukemia cells and that induction of autophagy prevents apoptotic cell death. The development of the resistance was observed to involve the enzymes that catabolize biogenic polyamines [ 113 ] and the PI3K/AKT/mTOR molecular pathway [ 170 ]. Doxorubicin resistance restores in response to mTOR inhibitors possibly because mTOR binds with ULK1 and suppresses its interaction with AMPK, thus inactivating ULK1 and inhibiting autophagy [ 171 ].…”

Section: Roles Of Autophagy and Apoptosis In Chemotherapy Resistance ...mentioning

confidence: 99%

Mechanisms of Survival of Cytomegalovirus-Infected Tumor Cells

2022

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Human cytomegalovirus (HCMV) DNA and proteins are often detected in malignant tumors, warranting studies of the role that HCMV plays in carcinogenesis and tumor progression. HCMV proteins were shown to regulate the key processes involved in tumorigenesis. While HCMV as an oncogenic factor just came into focus, its ability to promote tumor progression is generally recognized. The review discusses the viral factors and cell molecular pathways that affect the resistance of cancer cells to therapy. CMV inhibits apoptosis of tumor cells, that not only promotes tumor progression, but also reduces the sensitivity of cells to antitumor therapy. Autophagy was found to facilitate either cell survival or cell death in different tumor cells. In leukemia cells, HCMV induces a “protective” autophagy that suppresses apoptosis. Viral factors that mediate drug resistance and their interactions with key cell death pathways are necessary to further investigate in order to develop agents that can restore the tumor sensitivity to anticancer drugs.

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Section: Roles Of Autophagy and Apoptosis In Chemotherapy Resistance ...mentioning

confidence: 99%