Interactions between the tumor cells and bone marrow (BM) microenvironment promote survival, growth, and chemoresistance of acute myeloid leukemia (AML). The mTOR pathway plays a key role in mediating the AML-BM microenvironment interactions. Here, we report the anti-AML activity of a natural monomer extracted from the Chinese medicinal herb Evodia rutaecarpa, dihydroevocarpine. Our results showed that dihydroevocarpine-induced cytotoxicity, apoptosis, and G0/G1 arrest in AML cells, and inhibited the tumor growth in an AML xenograft model. Importantly, our study revealed that the dihydroevocarpine treatment inhibited the mTOR pathway via suppressing the mTORC1/2 activity, and thus overcame the protective effect of the BM microenvironment on AML cells. Taken together, our findings suggest that dihydroevocarpine could be used as a potential anti-AML agent alone or a therapeutic adjunct in AML therapy, particularly in the presence of the BM microenvironment.

中文翻译：

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用二氢依果胶碱靶向mTORC1 / 2可以诱导急性髓细胞性白血病的细胞毒性。

肿瘤细胞与骨髓（BM）微环境之间的相互作用促进了急性髓细胞性白血病（AML）的存活，生长和化学耐药性。mTOR途径在介导AML-BM微环境相互作用中起关键作用。在这里，我们报告了从中药吴茱E，二氢依果胶碱提取的天然单体的抗AML活性。我们的研究结果表明，在AML异种移植模型中，二氢依柔卡因诱导的细胞毒性，凋亡和G0 / G1在AML细胞中停滞，并抑制了肿瘤的生长。重要的是，我们的研究表明，二氢依果胶碱治疗通过抑制mTORC1 / 2活性而抑制了mTOR途径，从而克服了BM微环境对AML细胞的保护作用。在一起