Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is an aggressive cancer with a poor long term prognosis. Neo-adjuvant poly-chemotherapy followed by surgical resection remains the standard treatment, which is restricted by multi-drug resistance. If first-line therapy fails, disease control and patient survival rate drop dramatically. We aimed to identify alternative apoptotic mechanisms induced by the histone deacetylase inhibitor panobinostat in osteosarcoma cells. Saos-2, MG63 and U2-OS osteosarcoma cell lines, the immortalized human osteoblast line hFOB and the mouse embryo osteoblasts (MC3T3-E1) were treated with panobinostat. Real time viability and FACS confirmed the cytotoxicity of panobinostat. Cell stress/death related factors were analysed by RT-qPCR and western blot. Cell morphology was assessed by electron microscopy. 10 nM panobinostat caused cell viability arrest and death in all osteosarcoma and osteoblast cells. P21 up-regulation was observed in osteosarcoma cells, while over-expression of p73 was restricted to Saos-2 (TP53-/-). Survivin and Bcl-2 were suppressed by panobinostat. Endoplasmic reticulum (ER) stress markers BiP, CHOP, ATF4 and ATF6 were induced in osteosarcoma cells. The un-spliced Xbp was no further detectable after treatment. Autophagy players Beclin1, Map1LC3B and UVRAG transcripts over-expressed after 6 hours. Protein levels of Beclin1, Map1LC3B and p62 were up-regulated at 72 hours. DRAM1 was stable. Electron micrographs revealed the fragmentation and the disappearance of the ER and the statistically significant increase of autophagosome vesiculation after treatment. Panobinostat showed a synergistic suppression of survival and promotion of cell death in osteosarcoma cells. Panobinostat offers new perspectives for the treatment of osteosarcoma and other malignant bone tumours.
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PMID:Panobinostat mediated cell death: a novel therapeutic approach for osteosarcoma. 3025 Jun 45

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 IC10 to IC70. 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.
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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