Objective To investigate the effects of ketamine combined with gemcitabine on immune escape, tumor volume and MKK3/6 signaling pathway in brain glioma of rats. Methods Fifty SPF SD male rats were randomly divided into normal (NO), model (MO), ketamine (KM), gemcitabine (GT), ketamine combined with gemcitabine (KG) groups, with 10 in each group. Stereotaxic method was used to establish brain glioma modeling in MO, KM, GT and KG groups, while the model was not established in NO group. After establishing the modeling, the KM group was intraperitoneally injected with 100 mg/kg ketamine, the GT was intraperitoneally injected with 150 mg/kg gemcitabine, the KG with 100 mg/kg ketamine and 150 mg/kg gemcitabine, and NO and MO with the same volume of normal saline at the same time. HE staining was used to detect histopathologic morphology, ELISA and RT-PCR were used to detect immune escape related factors, and MKK3/6 protein expression was detected by Western blot. Results Compared with NO, the contents and mRNA expression of IL-4, IL-10 and TGF-β1 in MO groups were markedly increased (P<0.05), while the expression of MKK3/6 protein was significantly decreased (P<0.05). Compared with MO, the contents and mRNA expression of IL-4, IL-10 and TGF-β1 in KM, GT and KG groups were obvious decreased (P<0.05), while the tumor inhibition rate and MKK3/6 protein level were increased (P<0.05), however, which had no significant differences between GT and KM groups (P>0.05). The changes in KG were more significant than those in GT group (P<0.05). In NO, the brain tissue structure was normal and the cells were arranged neatly, while in group MO, the brain tissue was destroyed, and a large number of infiltrating tumor cells and lymphocytes could be seen, and the nuclear staining of cancer cells became deeper. Compared with group MO, the pathological structure of KM, GT and KG groups was significantly improved, and the nuclear staining of cancer cells became lighter. Conclusions Ketamine combined with gemcitabine has a significant effect on brain glioma, which can effectively inhibit immune escape, and regulate MKK3/6 expression.
Key words
Ketamine; /
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Gemcitabine; /
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Brain glioma; /
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Immune escape; /
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Tumor volume; /
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MKK3/6 signaling
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