abt-199 and oridonin

Acute myeloid leukemia (AML) is a recurrence-prone hematologic malignancy. The advent of molecularly targeted therapies provides new opportunities to enhance the effectiveness of AML treatments. Venetoclax, a selective inhibitor of the anti-apoptotic protein Bcl-2, has shown promising results; however, resistance often arises due to elevated expression of the Mcl-1 protein, among other factors. Overcoming this resistance to improve therapeutic outcomes is a pressing issue that requires further investigation. Studies have demonstrated that oridonin, by inhibiting AKT signaling that regulates Mcl-1 expression, can effectively suppress tumor cell growth. This study aims to investigate whether oridonin can synergistically enhance the anti-leukemic effects of venetoclax and explore the underlying mechanisms behind this effect.. Both venetoclax and oridonin individually exhibited inhibitory effects on AML cell proliferation, resulted in cell cycle arrest, and induced cell apoptosis. Moreover, combination of the two drugs resulted in a synergistic effect. We also observed that oridonin inhibited AKT phosphorylation, upregulated the expression of Bim and Bax proteins, facilitated Mcl-1 degradation, and enhanced the apoptotic effects of venetoclax in AML cells. Finally,. Oridonin and venetoclax synergistically promote AML cell apoptosis by inhibiting AKT signaling.

Topics: Animals; Apoptosis; Cell Line, Tumor; Humans; Leukemia, Myeloid, Acute; Mice; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2