Decreasing bone marrow (BM) microvessel density and circulating angiogenic cytokine levels are promising strategies for the treatment of relapsed and resistant acute myeloid leukemia (AML). Previous studies have reported that wogonoside could inhibit the progression of AML and suppress angiogenesis in a solid tumor, but the correlation of these two effects was ignored. In this research, we determined whether wogonoside could inhibit angiogenesis in this hematologic malignancy. We found that wogonoside could inhibit tumor growth and progression, and prolong the survival of nude mice inoculated with U937/MDR. Besides, reducing BM angiogenesis might cause therapeutic effect against resistant AML. Therefore, coculture between AML cells and BM stromal cells was established to imitate their crosstalk. Then, the effect of wogonoside on BM angiogenesis was tested in vitro and in vivo. We found that wogonoside could suppress microvessel formation in the chicken chorioallantoic membrane assay model and matrigel plug assay. The mechanism research revealed that wogonoside could block the JAK2-STAT3 pathway in AML cells and stromal cells to break their positive feedback. We detected several cytokines related to AML or angiogenesis and found that secreted interleukin-8 was a significant angiogenic cytokine to induce BM angiogenesis. These findings supported that new diagnostics and promising treatment strategies could be developed in relapsed and resistant AML patients.
Keywords: STAT3; acute myeloid leukemia (AML); bone marrow (BM) angiogenesis; interleukin-8 (IL-8); wogonoside.
© 2018 Wiley Periodicals, Inc.