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Pivot Concepts:
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Target Concepts:
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Query: UNIPROT:P11021 (
BiP
)
2,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Osteosarcoma is a common primary malignant tumor of bone, and the poor prognosis and low 5-year survival rate have not improved for three decades. The present study aimed to study the effect a combination of
celastrol
and cisplatin on the human osteosarcoma cell line U-2OS, and to investigate the mechanism by which
celastrol
/cisplatin induces the apoptosis of osteosarcoma cells. MTT and Annexin V-FITC/PI assays were used to evaluate the effects of combined
celastrol
/cisplatin on growth and apoptosis, respectively, in U-2OS cells. Morphological changes accompanying cell growth inhibition were observed using a fluorescence microscope. Combination index (CI) analysis was used to evaluate the combinatorial effects of
celastrol
/cisplatin treatment. Western blotting was used to quantify the expression of apoptosis-associated proteins. It was identified that
celastrol
/cisplatin inhibited the growth of U-2OS cells in a dose-dependent manner. CI analysis revealed that combined
celastrol
/cisplatin demonstrated a synergistic effect in U-2OS cells, with CIs ranging from 0.80 to 0.97 at effect levels from IC
10
to IC
70
. In addition, it was observed that
celastrol
/cisplatin upregulated the expression of Bcl-associated X protein, cytochrome
c
, caspase-3 and C/EBP homologous protein, and downregulated the expression of Bcl-2, poly(ADP-ribose) polymerase,
78 kDa glucose-regulated protein
and caspase-9, whereas the expression of caspase-8 remained unchanged. To conclude,
celastrol
/cisplatin induced apoptosis in U-2OS cells via the mitochondrial and endoplasmic reticulum pathways, particularly in the former.
Celastrol
/cisplatin therefore exhibits potential as a novel therapeutic combination for the treatment of osteosarcoma.
...
PMID:Efficacy of celastrol combined with cisplatin in enhancing the apoptosis of U-2OS osteosarcoma cells via the mitochondrial and endoplasmic reticulum pathways of apoptosis. 3086 64
