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author:

Huang, Z.-Y. (Huang, Z.-Y..) [1] | Gan, D.-H. (Gan, D.-H..) [2] | Chen, Y.-Y. (Chen, Y.-Y..) [3] | Chen, H.-J. (Chen, H.-J..) [4] | Lin, M.-H. (Lin, M.-H..) [5] | Yirga, S.K. (Yirga, S.K..) [6] | Hu, J.-D. (Hu, J.-D..) [7]

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Abstract:

题目: 黄芩苷衍生物02-036对Burkitt淋巴瘤CA46细胞株的作用及相关机制. 目的: 探讨黄芩苷(Baicalin)衍生物02-036对人Burkitt淋巴瘤CA46细胞株的增殖、凋亡的影响及其相关机制. 方法: 应用MTT法检测和绘制细胞生长曲线;细胞集落形成实验检测黄芩苷衍生物02-036对CA46细胞增殖的影响;AnnexinV-FITC/PI双染流式细胞术检测02-036对细胞凋亡的影响;DNA倍体分析(DNA ploidy analysis)检测02-036对细胞周期的影响;Western blot检测增殖及凋亡相关蛋白BCL-2、Procaspase-9、Procaspase-3、PARP和C-MYC表达水平. 结果: 细胞生长曲线结果显示黄芩苷衍生物02-036对CA46细胞株有明显的抑制增殖作用,并且呈量效和时效关系(r=0.963,r=0.992),48 h半数抑制浓度(IC50)为(6.04±0.11) μmol/L。细胞集落形成实验显示,02-036作用 CA46细胞后,细胞集落形成能力明显降低,并在一定范围内呈量效关系(r=-0.967)。Annexin V-FITC/PI双染流式细胞术分析结果表明,02-036能有效诱导CA46细胞凋亡,并且在一定范围内,细胞凋亡率随着药物作用浓度的增高而增加(r=0.959)。DNA倍体分析检测显示02-036能将CA46的细胞周期阻滞于S期。不同浓度的02-036作用于CA46细胞后,BCL-2、Pro-caspase-9、Pro-caspase-3、PARP和C-MYC的表达逐渐下调,而Cleaved-PARP表达逐渐上调,并呈现量效关系(r值分别为-0.990、-0.939、 -0.971、-0.967、-0.936和0.920). 结论: 黄芩苷衍生物02-036能有效抑制CA46细胞增殖,诱导其凋亡,在一定范围内呈时效和量效关系;其作用机制可能与BCL-2、Pro-caspase-9、Pro-caspase-3、PARP 及C-MYC的表达下调有关.OBJECTIVE: To investigate the effect of baicalin derivative 02-036 on proliferation and apoptosis human Burkitt lymphoma cell line CA46 and its related mechanisms. METHODS: The MTT assay and cell colony formation assay were used to measure the growth inhibition of CA46 cells after 02-036 treatment. The flow cytometry with AnnexinV-FITC/PI double staining was employed to detect the apoptosis induction effect of 02-036 on CA46 cells. Cell cycle distribution of CA46 cells was estimeted by using DNA ploid analysis. Western blot was used to determine the changes of apoptosis-related proteins, including C-MYC, BCL-2, Procaspase-9, Procaspase-3, PARP and Cleaved-PARP. RESULTS: Baicalin derivative 02-036 obviously inhibited the proliferation of CA46 cells, with dose- and time-dependent manner (r=0.963, r=0.992). The averaged IC50 value of CA46 cells was (6.04±0.11) μmol/L after 48-hour treatment. Low concentration of 02-036 could significantly inhibit the colony formation of CA46 cells. Flow cytometry analysis confirmed that 02-036 could effectively induce CA46 cell apoptosis. The apoptosis rate correlated with drug concentrations (r=0.959). Also, DNA ploid analysis showed that the cell cycle of CA46 was arrested in the S phase. The expression levels of BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC proteins decreased with a 02-036-dose dependent manner (r values were -0.990, -0.939, -0.971 and -0.967, respectively). In contrast, the expression level of cleaved-PARP increased with the same manner (r=0.920). CONCLUSION: Baicalin derivative 02-036 can effectively inhibit the proliferation and induce apoptosis of CA46 cells, and its related mechanisms may be correlated with the down-regulation of apoptosis-related molecule expression levels, such as BCL-2, Pro-caspase-9, Pro-caspase-3, PARP and C-MYC.

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Community:

  • [ 1 ] [Huang, Z.-Y.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China
  • [ 2 ] [Huang, Z.-Y.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian
  • [ 3 ] [Gan, D.-H.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China
  • [ 4 ] [Gan, D.-H.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian
  • [ 5 ] [Chen, Y.-Y.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China
  • [ 6 ] [Chen, Y.-Y.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian
  • [ 7 ] [Chen, H.-J.]School of Chemistry and Chemical Engineering,Fuzhou University,Fuzhou 350108,Fujian Province,China
  • [ 8 ] [Lin, M.-H.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China
  • [ 9 ] [Lin, M.-H.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian
  • [ 10 ] [Yirga, S.K.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian Province,China
  • [ 11 ] [Yirga, S.K.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian
  • [ 12 ] [Hu, J.-D.]Fujian Institute of Hematology,Fujian Provincial Key Laboratory of Hematology,Fujian Medical University Union Hospital,Fuzhou 350001,Fujian

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Source :

Zhongguo shi yan xue ye xue za zhi

ISSN: 1009-2137

CN: 11-4423/R

Year: 2019

Issue: 5

Volume: 27

Page: 1497-1503

Cited Count:

WoS CC Cited Count: 0

SCOPUS Cited Count: 2

ESI Highly Cited Papers on the List: 0 Unfold All

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30 Days PV: 0

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