胡仁智,夏敏,赵世巧

• 1:重庆市中医院

摘要(Abstract)：

目的 探讨雷公藤甲素引起急性髓性白血病细胞凋亡的相关分子机制。方法 使用不同浓度雷公藤甲素处理HL-60,U937细胞24 h后用MTT法检测细胞存活率，流式细胞仪检测凋亡，Western blotting检测P62、LC3B、Caspase-3、PARP-1及细胞色素C，联用自噬抑制剂3-MA预处理U937细胞后流式细胞仪检测凋亡，自噬以及凋亡相关蛋白用蛋白印迹法检测。结果 雷公藤甲素对HL-60、U937细胞的IC50值分别为(33.86±2.84)、(36.67±3.15) nmol/L，雷公藤甲素可明显诱导HL-60、U937细胞凋亡，差异有统计学意义(P<0.01)。雷公藤甲素可降低自噬降解底物蛋白P62表达，自噬标志蛋白LC3B-II表达上调，说明雷公藤甲素可诱导自噬。自噬抑制剂3-甲基腺嘌呤预处理细胞，阻断凋亡信号通路的激活，雷公藤甲素诱导的白血病细胞凋亡明显减少。结论 雷公藤甲素可促进自噬体降解进而激活凋亡信号通路，诱导急性髓性白血病细胞凋亡。

关键词(KeyWords)： 急性髓性白血病;雷公藤甲素;自噬;凋亡

Abstract:

Keywords:

基金项目(Foundation): 成都中医药大学2020年度“杏林学者”医院专项(YYZX2020046)

作者(Author): 胡仁智,夏敏,赵世巧

参考文献(References)：

• [1] Csizmar CM,Kim DH,Sachs Z. The role of the proteasome in AML[J]. Blood Cancer Journal,2016(6):e503.
• [2] De Necochea-Campion R. Aberrant splicing and drug resistance in AML[J]. Journal of Hematology&Oncology,2016,9(1):85.
• [3]邓艳芳，赖慈爱，代喜平.从“固护脾肾元气”论治急性白血病化疗后骨髓抑制初探[J].中国中医急症，2021,30(12):2234-2236.
• [4] Yanchun M,Yi W,Lu W,et al. Triptolide prevents proliferation and migration of esophageal squamous cell cancer via MAPK/ERK signaling pathway[J]. European Journal of Pharmacology,2019,3(15):851.
• [5] Zhang Z,Sun C,Zhang L,et al. Triptolide interferes with XRCC1/PARP1-mediated DNA repair and confers sensitization of triple-negative breast cancer cells to cisplatin[J]. Biomedicine&Pharmacotherapy,2019,109:1541-1546.
• [6] Xue M. Triptolide attenuates renal tubular epithelial-mesenchymal transition via the MiR-188-5p-mediated PI3K/Akt pathway in diabetic kidney disease[J]. International Journal of Biological Sciences,2018,14(11):1545-1557.
• [7]赖芸，陈子珺.有毒中药抗白血病的作用及机制研究进展[J].中成药，2016,38(4):875-879.
• [8]史远飞.低剂量雷公藤甲素增强BET蛋白拮抗剂JQ1对急性髓系白血病细胞的杀伤作用及分子机制[D].厦门：厦门大学，2019.
• [9]姜秀星，傅若秋，高宁.千金藤素协同多柔比星逆转K562/ADR耐药的分子机制研究[J].第三军医大学学报，2018,40(23):2154-2161
• [10] Foran JM. Frontline therapy of AML:should the older patient be treated differently[J]. Current Hematologic Malignancy Reports,2014,9(2):100-108.
• [11]张晓丹，周永明，严静贤.中医药治疗急性髓系白血病的研究进展[J].中国中医急症，2020,29(5):925-929.
• [12]陈玉，蔡恩照，张隽瑜，等.从“毒”论治急性白血病初探[J].中国中医急症，2020,29(5):916-918.
• [13] Rowe JM. AML in 2016:Where we are now[J]. Best Practice&Research Clinical Haematology,2016,29(4):315-319.
• [14] Molica M. Maintenance therapy in AML:The past,the present and the future[J]. American Journal of Hematology,2019,(94):1254-1265.
• [15] Yeung CCS,Radich J. Predicting chemotherapy resistance in AML[J]. Current Hematologic Malignancy Reports,2017,12(6):530-536.
• [16] Winer ES,Stone RM. Novel therapy in Acute myeloid leukemia(AML):moving toward targeted approaches[J]. Therapeutic Advances in Hematology,2019,10:1-8.
• [17] Dower CM. Mechanisms and context underlying the role of autophagy in cancer metastasis[J]. Autophagy,2018,14(7):1110-1128.
• [18] Fitzwalter BE,Thorburn A. FOXO3 links autophagy to apoptosis[J]. Autophagy,2018,14(8):1467-1468.
• [19] Nazio F,Cecconi F. Autophagy up and down by outsmarting the incredible ULK[J]. Autophagy,2017,13(5):967-968.
• [20] Racanelli AC. Autophagy and inflammation in chronic respiratory disease[J]. Autophagy,2018,14(2):221-232.
• [21] Yao J. Inhibiting autophagy reduces retinal degeneration caused by protein misfolding[J]. Autophagy,2018,14(7):226-1238.
• [22] Yu L,Chen Y,Tooze SA,et al. Autophagy pathway:Cellular and molecular mechanisms[J]. Autophagy,2017,14(2):207-215.