Hyperactivation of AKT plays a critical role in the survival and proliferation of cancer cells. However, the molecular mechanisms underlying AKT activation remain elusive. Here, we tested the effect of γ-synuclein, a member of the synuclein family of proteins, on the activation of AKT. We show that the expression level of γ-synuclein is increased in non-small cell lung cancer (NSCLC) tissues. γ-Synuclein binds to the protein kinase domain of AKT and promotes its phosphorylation. Overexpression of γ-synuclein in H157 cells enhances cell proliferation and protects the cells from staurosporine-induced cytotoxicity. Knockdown of γ-synuclein attenuates AKT activation and cell proliferation induced by epidermal growth factor. The effect of γ-synuclein is abolished when AKT is depleted. Thus, γ-synuclein promotes cell survival and proliferation via activating AKT and may play a causal role in the pathogenesis of NSCLC.
This study investigated the protective effect of crocetin from Crocus sativus L. on myocardial ischemia-reperfusion injury (MORO) in rats. Sixty SD rats were randomly divided into sham-operated, model, and low-, medium-and high-dose crocetin groups. Later 3 groups were intragastrically administrated with 10, 20 and 40 mg/kg crocetin from Crocus sativus L., respectively, for 1 week. Dn the 8th day, the MORO model was established in the later 4 groups. The blood biochemical indexes, hemodynamic indexes, myocardial infarct size, myocardial antioxidant indexes and myocardial expressions of B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), serine/threonine kinase (Akt) and phosphorylated Akt (p-Akt) protein were determined. Results showed that, compared with model group, in high-dose crocetin group the left ventricular systolic pressure, +dp/dt max and-dp/dt max , myocardial superoxide dismutase and glutathione peroxidase levels, and myocardial Bcl-2/Bax ratio and p-Akt/Akt ratio were significantly increased, and the left ventricular end diastolic pressure, myocardial infarct size, serum lactate dehydrogenase, creatine kinase-MB, cardiac troponin O, tumor necrosis factor-α, interleukin-1β, interleukin-6 and malondialdehyde levels were significantly decreased (all P < 0.05). On conclusion, crocetin from Crocus sativus L. has protective effects on MORO in rats.
The effects of erlotinib combined with celecoxib in a lung cancer xenograft model were here explored with a focus on possible mechanisms. A xenotransplanted lung cancer model was established in nude mice using the human lung cancer cell A549 cell line and animals demonstrating tumour growth were randomly divided into four groups: control, erlotinib, celecoxib and combined (erotinib and celecoxib). The tumor major axis and short diameter were measured twice a week and after 40 days tissues were collected for immunohistochemical analyses of Bcl-2 and Bax positive cells and Western-blotting analyses for the epidermal growth factor recepto (EGFR), P-EGFR, and cyclooxygenase-2 (COX-2). Tumor size in the combined group was smaller than in the others (p<0.01) and the percentage of Bcl-2 positive cells was fewer in most cases (p<0.01), while that of Bax positive cells was greater than in the erlotinib and celecoxib groups (P>0.05). Western blotting showed decreased expression of P-EGFR and COX-2 with both erlotinib and celecoxib treatments, but most pronouncedly in the combined group (P<0.05). Simultaneous blockage of the EGFR and COX-2 signal pathways exerted stronger growth effects in our human xenotransplanted lung cancer model than inhibition of either pathway alone. The anti-tumor effects were accompanied by synergetic inhibition of tumor cell apoptosis, activation of p-EGFR and expression of COX-2.
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