Myeloid ecotropic viral integration site-1 inhibition promotes apoptosis, suppresses proliferation of acute myeloid leukemia cells, accentuates the effects of anticancer drugs.

Yinglan Jin, Jinghua Wang, Mingming Zhao, Jingyi Lin, Luojia Hong

Bioengineered 2022 Mar

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To investigate the effects of myeloid ecotropic viral integration site-1 (MEIS1) on the proliferation and apoptosis of acute myeloid leukemia (AML) cells and the anticancer effects of the drug, we screened Kasumi-6, KG-1, and Kasumi-1 cells using quantitative reverse transcription polymerase chain reaction. Kasumi-6 and Kasumi-1 cells were subjected to human antigen R (HuR)-mediated interference (IV). Hexokinase 2 (HK2) expression and phosphorylation of protein kinase B (p-AKT) and mammalian target of rapamycin (p-mTOR) were observed with Western blotting. Cell proliferation was assessed using Cell Counting Kit-8, apoptosis was examined using Hoechst 33,258 staining, and glucose uptake was detected with a colorimetric biochemical assay kit. We found that, among the three cell lines tested, MEIS1 expression was highest in Kasumi-1 cells, which were therefore selected for subsequent experiments. Kasumi-1 cells receiving IV showed significantly decreased proliferation (p < 0.05) and increased apoptosis compared to the control group. Compared with the controls, IV significantly increased the expression of HK2, p-AKT, p-mTOR, multidrug resistance-associated protein 1 and P-glycoprotein (P < 0.05), but decreased glucose uptake. Treatment with adriamycin, daunorubicin and imatinib resulted in a progressive increase in inhibition of cell proliferation, with the IV group showing the highest inhibition rate among the three groups (P < 0.05). Thus, inhibition of MEIS1 activity promoted apoptosis, inhibited the proliferation of Kasumi-1 and Kasumi-6 cells, and increaseed the anticancer effect of the drugs, suggesting that inhibition of MEIS1 may be a potential strategy for the treatment of AML.

Citation

Yinglan Jin, Jinghua Wang, Mingming Zhao, Jingyi Lin, Luojia Hong. Myeloid ecotropic viral integration site-1 inhibition promotes apoptosis, suppresses proliferation of acute myeloid leukemia cells, accentuates the effects of anticancer drugs. Bioengineered. 2022 Mar;13(3):5700-5708