Clinical and experimental pharmacology & physiology
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Clin. Exp. Pharmacol. Physiol. · Jan 2013
Effects of epidermal growth factor receptor and phosphatase and tensin homologue gene expression on the inhibition of U87MG glioblastoma cell proliferation induced by protein kinase inhibitors.
The aim of the present study was to analyse the antiproliferative effects and mechanisms of action of protein kinase inhibitors (PKIs) in human glioblastoma multiforme (GBM) cells with different epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) status. The GBM cell models were established by transfection of plasmids carrying wild-type EGFR, mutated EGFRvIII or PTEN and clonal selection in U87MG cells. Phosphatidylinositol 3-kinase (PI3-K)/AKT pathway-focused gene profiles were examined by real-time polymerase chain reaction-based assays, protein expression was evaluated by western blotting and the antiproliferative effects of PKI treatment were determined by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in GBM cells. ⋯ Concurrent inhibition of mTOR and ribosomal protein s6 activity may underlie the inhibition of GBM proliferation by PKI. In conclusion, overexpression of EGFR or EGFRvIII, accompanied by a loss of PTEN, contributed to the activation of multiple intracellular signalling pathways in GBM cells. Rigorous examination of biomarkers in tumour tissues before and after treatment may be necessary to determine the efficacy of PKI therapy in patients with GBM.
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Clin. Exp. Pharmacol. Physiol. · Jan 2013
Effects of betamethasone on neuropathic pain in a rat spare nerve injury model.
The aim of the present study was to examine the effect of glucocorticoids on neuropathic pain using a rat spare nerve injury (SNI) model. Eighty rats were treated divided into the following groups: (i) a sham-operated group; (ii) a group subjected to SNI (S); (iii) a group subjected to SNI and administered 4 μg betamethasone intrathecally (D1); and (iv) a group subjected to SNI and administered 1 mg betamethasone at the site of nerve injury (D2). The mechanical withdrawal threshold (MWT) and thermal withdrawal duration (TWD) were measured 1 day before and the 1, 3, 7 and 14 days after SNI. ⋯ Levels of TNF-α and IL-1β were significantly lower in the D1 and D2 groups compared with the S group at all time points after surgery (P < 0.05). Betamethasone suppressed astrocyte activation and increases in TNF-α and IL-1β levels in a rat model of neuropathic pain. Local injection of betamethasone resulted in smaller increases in spinal GR expression and more pronounced improvement in pain behaviour compared with intrathecal injection.