Inhibitory Effect of PKC412 Against Human Acute Leukemia Cell Line HL-60 Cells / 中国实验血液学杂志
Journal of Experimental Hematology
; (6): 62-67, 2021.
Article
em Zh
| WPRIM
| ID: wpr-880032
Biblioteca responsável:
WPRO
ABSTRACT
OBJECTIVE@#To explore the effects and mechanisms of PKC412 inhibitor on proliferation and apoptosis of HL-60 cell line.@*METHODS@#CCK-8 assay was used to detect the effect of PKC412 on the proliferation of HL-60 cells at different concentrations; Wright-Giemsa staining was used to estimated the effect of PKC412 on the apoptosis of HL-60 cells; the mRNA expression of BCL-2 and P53 genes was detected by qRT-PCR, the expression of BCL-2 and P53 proteins was detected by Western blot. HL-60 cells were injected into mouse caudal vein to construct acute myeloid leukemia model, PKC412 was administered to tail vein for 31.25 nmol/kg, normal saline was injected into the same site of the mice as control group, and the inhibitory effect of PKC412 on HL-60 cells in mice was observed. ELISA assay was used to detect the effect of PKC412 on the inflammatory factors of TNF-α and TGF-β in tumor mice.@*RESULTS@#PKC412 could inhibit the proliferation of HL-60 cell, which was in a dose dependent manner(r=0.9973) (IC50 was 0.31 μmol/L), and induce apoptosis of HL-60 cells. After HL-60 cell was treated by PKC412 for 48 h the expression of BCL-2 gene was down regulated(0.417±0.044 vs 0.933±0.033, t=9.347, P0.05) as compared with control group. And the expression of BCL-2 protein was decreased, while the expression of P53 protein was increased. PKC412 could inhibited the growth of HL-60 tumor cells in vivo, the survival rate of mice after administration was 50% and the weight was increased as compared with that in control group(18.02±0.403 g vs 16.44±0.562 g, t=2.272, P=0.0356). The secretion of TNF-α and TGF-β cytokine in serum and spleen cells in PKC412 group was significantly lower than that in control group (P<0.05).@*CONCLUSION@#PKC412 can induce apoptosis of HL-60 cells by inhibiting the expression level of BCL-2 gene, PKC412 administration in vivo can inhibit the growth of the tumors.
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Índice:
WPRIM
Assunto principal:
Leucemia Mieloide Aguda
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Apoptose
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Células HL-60
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Estaurosporina
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Proteínas Proto-Oncogênicas c-bcl-2
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Proliferação de Células
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
Zh
Revista:
Journal of Experimental Hematology
Ano de publicação:
2021
Tipo de documento:
Article