The effect of Gö6976 on chronic myeloid leukemia in vitro and in vivo.
2021
Objectives: Chronic myeloid leukemia (CML) is a malignant tumor of the blood system. Go6976, as a type of indolocarbazole and shows strong antitumor effects, but there have been no reports on the effect of Go6976 on CML. The objectives of this research were: (1) to explore the impact of Go6976 on CML in vitro and in vivo; and (2) to explore the drug toxicity of Go6976 to normal cells and animals.Methods:K562 cells and CML mice were used to explore the effect of Go6976 on CML. Peripheral blood mononuclear cells (PBMCs), CD34+ cells, and healthy mice were used to explore the drug toxicity of Go6976.Results: Cell experiments showed that Go6976 could inhibit the proliferation of K562 cells and enhance the inhibitory effects of imatinib at 5 μM and 10 μM, but it had little effect on CD34+ cells or PBMCs at concentrations less than 5 μM. Animal experiments showed that 2.5 mg/kg Go6976 could effectively inhibit the development of CML in mice, and it had almost no effects on healthy mice at 2.5 mg/kg and 10 mg/kg.Discussion: Because of the direct inhibitory effect of Go6976 on CML and its pharmacological enhancement effect on imatinib, it is foreseeable that Go6976 could become a new type of anti-CML medicine. And the further research is needed.Conclusion: Our findings verified that Go6976 could effectively inhibit CML in vitro and in vivo, and it is almost nontoxic to hematopoietic cells, immune cells, and healthy mice.
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