[Effect of Low-Dose Triptolide and Sorafenib Alone and Their Combination on AML Cell Line MV411 and the Pathway of STAT5]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Aug;27(4):1088-1093. doi: 10.19746/j.cnki.issn.1009-2137.2019.04.016.
[Article in Chinese]

Abstract

Objective: To investigate the effects of inhibiting proliferation and inducing apoptosis of low-dose triptolide and sorafenib alone or in combination on FLT3-ITD+ acute myeloid leukemia cell line MV4-11 and STAT5 pathway.

Methods: The MV4-11 cells were treated with low dose triptolide(IC20) and sorafenib(IC50) alone or in combination for 48 hours. The cell proliferation and inhibition were detected by using CCK-8 kit, the cell apoptosis was detected by flow cytometry, the expression of FLT3,STAT5 in mRNA and protein levels was detected by RT-PCR and Western blot respectively.

Results: The treatment of MV4-11 cells with low dose triptolide and sorafenib alone and in combination for 48 hours could inhibit cell proliferation and induce cell apoptosis, moreover the inhibitory rate and apoptotic rate of MV4-11 cells in drug-combination group both were higher than those in single drug group. The mRNA expression and protein expression of FLT3,STAT5 signaling pathway in drug combination group were significantly lower than those in single drug group.

Conclusion: Low-dose triptolide combined with sorafenib can synergistically inhibit the proliferation and induce the apoptosis of MV4-11 cells, which may be related with the inhibition of FLT3 and STAT5 pathway.

题目: 低剂量雷公藤内酯醇和索拉非尼单药及其联用对AML细胞株MV411及其STAT5信号通路的作用.

目的: 探讨低剂量雷公藤内酯醇、索拉非尼单药及二者联合对FLT3-ITD突变阳性人急性髓系白血病细胞株 MV4-11 细胞的抑制增殖和诱导凋亡的作用,以及对STAT5通路的影响.

方法: 采用低剂量雷公藤内酯醇 (IC20)和索拉非尼(IC50)单药及二者联合作用于MV4-11细胞,在48 h时间点,用CCK-8试剂盒测定各组细胞的增殖抑制情况,用流式细胞术检测凋亡率,采用RT-PCR法测定FLT3、STAT5 mRNA表达水平,Western blot法测定 FLT3、STAT5、P-STAT5蛋白的表达水平.

结果: 雷公藤内酯醇、索拉非尼单药及二者联合用药48 h对MV4-11细胞株有抑制增殖和诱导凋亡的作用,联合用药组抑制率及凋亡率均高于单药组,联合用药组FLT3、STAT5通路基因及蛋白的表达显著低于单药组.

结论: 低剂量雷公藤内酯醇联合索拉非尼可协同抑制MV4-11细胞的增殖及诱导其凋亡,其机制可能与抑制FLT3及STAT5 通路有关.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Diterpenes
  • Epoxy Compounds
  • Humans
  • Leukemia, Myeloid, Acute*
  • Phenanthrenes
  • STAT5 Transcription Factor
  • Sorafenib
  • fms-Like Tyrosine Kinase 3

Substances

  • Diterpenes
  • Epoxy Compounds
  • Phenanthrenes
  • STAT5 Transcription Factor
  • triptolide
  • Sorafenib
  • fms-Like Tyrosine Kinase 3