中国药理学通报2026，Vol.42Issue(1)：49-55,7.DOI:10.12360/CPB202507013
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
Tocilizumab inhibits IL-6-JAK-STAT3 signaling to reverse bone marrow stromal cell-mediated AML chemotherapy resistance
摘要
Abstract
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.关键词
急性髓细胞白血病/骨髓基质细胞/共培养模型/白细胞介素6/托珠单抗/化疗耐药Key words
acute myeloid leukemia/bone marrow stromal cell/co-culture model/interleukin 6/tocili-zumab/chemotherapy resistance分类
医药卫生引用本文复制引用
肖启荣,李晓静,林碧寸,林凯婷,林晓斌,王匡非,李暐,陈萍..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[J].中国药理学通报,2026,42(1):49-55,7.基金项目
国家自然科学基金资助项目(No 81800136) （No 81800136）
国家临床重点专科建设项目(No闽卫医政2021-76号) （No闽卫医政2021-76号）
福建省恶性血液病临床医学研究中心(No 2020Y2006) （No 2020Y2006）
福建省卫生健康中青年骨干人才培养项目(No 2021GGA019) （No 2021GGA019）
福建省科技创新联合资金攀登项目(No 2020Y9097) （No 2020Y9097）
