Abstract
Abstract Autophagy is one of the key catabolic cellular processes that ensures proteostasis and elimination of defective proteins and cell organelles. Autophagy has been shown to contribute to the formation of resistance of cancer cells to chemotherapeutic drugs, and the use of autophagy inhibitors as part of combination therapy is considered a promising strategy for increasing the effectiveness of treatment of various types of cancer. Methyltransferase Set7/9 is an enzyme that methylates histones H1, H2A, H2B, and H3, as well as proteins such as p53, E2F1, PARP1, and NFkB, etc. It has been shown that Set7/9 is a regulator of carcinogenesis, in particular affecting the formation and progression of non-small-cell lung cancer. We demonstrate that suppression of the Set7/9 methyltransferase leads to decreased levels of autophagy in H1299 cells, and this contributes to their sensitization to the genotoxic anticancer drugs doxorubicin and etoposide. In addition, the autophagy inhibitor chloroquine has a synergistic effect in combination with doxorubicin and etoposide and significantly reduces their effective concentrations, especially for more treatment-resistant cells characterized by high levels of Set7/9 expression.