托珠单抗通过抑制IL-6-JAK-STAT3信号逆转骨髓基质细胞介导的AML化疗耐药OA

Aim To study tocilizumab(TCZ)-medi-ated reversal of chemotherapy resistance in acute my-eloid leukemia(AML)cells by blocking the IL-6/JAK/STAT3 signaling pathway in the bone marrow microen-vironment.Methods An in vitro co-culture system was established using AML cell lines(U937 and HL-60)and HS-5 bone marrow stromal cells,followed by assessment of IL-6/JAK/STAT3 signaling pathway acti-vation through Western blot.Subsequent experiments utilized IL-6-knockdown HS-5 cells and TCZ to target this pathway in co-cultured AML cells,with drug sen-sitivity to Ara-C assessed by CCK-8 and AnnexinV-APC/7-AAD assays.In vivo validation was performed using AML xenograft models to evaluate TCZ's syner-gistic effect with Ara-C.Results In an adhesion co-culture system,IL-6 secreted by HS-5 cells activated the STAT3 signaling pathway in AML cells.This acti-vation was effectively suppressed by either IL-6 knock-down or TCZ treatment,which inhibited JAK2/STAT3 phosphorylation.Consistently,TCZ treatment signifi-cantly sensitized AML cells to Ara-C chemotherapy in both in vitro and in vivo settings.Conclusion TCZ enhances AML cell sensitivity to Ara-C by targeting the IL-6/JAK/STAT3 signaling pathway.