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Glioma is a malignant tumor with extremely high rates of recurrence. Clinically ，with the prolongation of the use of chemotherapy drugs ，the drug resistance of glioma cells to chemotherapy drugs is also increasing ，which eventually leads to poor prognosis and shortens overall survival time of patients. It is well known that the development of drug resistance involves multiple mechanisms，including drug transport metabolism ，apoptosis，DNA damage repair ，autophagy，variation of cancer stem cells and epithelial mesenchymal transition. Abnormal expression of circular RNA （circRNA），a novel RNA molecule with unique stability and tissue specificity ，has been shown by more and more evidence to play a crucial regulatory role in the development of drug resistance in glioma. This paper systematically reviews the mechanism of multiple drug resistance in glioma ，and focuses on the role and molecular mechanism of circRNA regulating temozolomide-resistance in glioma. At the same time ，the potential function of circRNA as a new therapeutic target is prospected ，in order to provide an objective theoretical basis for the development of new therapeutic methods.
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Objective To investigate the effect of ganoderic acid A( GA-A) on apoptosis, invasion and KDR expression of human U251 cells.Methods Ganoderic acid A( GA-A) was prepared, human U251 cells were treated with 0.1, and 0.5 mmol/L GA-A, and the experiment was divided into blank control, low concentration and high concentration group.The expressions of KDR mRNA and KDR protein was assayed by RT-PCR and Western blot.The effect of GA-A on the proliferation and invasion capability of U251 cells was determined by CCK-8 and transwell assay in vitro, respectively.Flow cytometry was used to detect the influence of GA-A on the cell cycle and apoptosis of U251 cells, and TUNEL staining was detected the cell apoptosis too.Results Compared with the control group, KDR mRNA and protein expression of high concentration and low concentration group were significantly decreased(P <0.05), GA-A can significantly reduce the cell growth rate, reduce the proportion of cells in G1 phase and increase the proportion of S phase and G2 /M phase,cells apoptosis was significantly increased in the high concentration and low concentration group ( P <0.01), and cells proliferation and invasion was significantly decreased (P <0.05).Compared with low concentration group, the high concentration group induce cell apoptosis and inhibit the expression of KDR more significant (P <0.05). Conclusions Ganoderma acid A can induce apoptosis in U251 cells, inhibit proliferation and invasion, and can inhibit the expression of KDR mRNA and protein, which may be one of the mechanisms of anti-tumor.
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BACKGROUND:It has been demonstrated that there are different expressions of fatty acid binding proteins (FABPs) in most malignant tumors such as breast cancer, prostate cancer, liver cancer, lung carcinoma and bladder carcinoma;therefore, FABPs are closely related to the occurrence, metastasis, invasion and drug resistance of malignant tumors. OBJECTIVE:To investigate the effects of fatty acid binding protein-5 (FABP-5) silencing on the proliferation, invasion and apoptosis of U251 cel s (human glioma cel s). METHODS:siRNA molecules targeting the mRNA of FABP-5 was designed and chenical y synthesized, which was transiently transfected into U251 cel s. U251 cel s were divided into three groups:Lv-shRNA-FABP-5 was added into FABP-5-shRNA group, LV-shRNA-NC added into negative control group, and blank control group underwent normal culture. mRNA and protein expressions of FABP-5 were detected by RT-PCR and western blot assay, respectively. The cel proliferation in vitro was determined by cel counting kit-8 assay, the cel cycle, apoptosis and expressions of CD44+and CD133+were detected by flow cytometry, and the apoptosis was observed using TUNEL staining. RESULTS AND COUNCLUSION:mRNA and protein expressions of FABP-5 in the FABP-5-shRNA group were significantly lower than those in the negative control and blank control groups. Compared with the negative control and blank control groups, the cel growth rate was significantly decreased, the cel cycle arrested in the G0/G1 phase, and the cel number in the S phase was decreased, and moreover, the proportion of CD44+/CD133+expression was significantly decreased in the FABP-5-shRNA group (P<0.05). Besides, compared with the negative control and blank control groups, the apoptosis rate was significantly increased, and the cel proliferation and invasiveness were significantly decreased in the FABP-5-shRNA group (P<0.05). In conclusion, it is possible that FABP-5 directly or indirectly regulates the cel cycle and apoptosis of glioma cel s, and its expression changes share a close relationship with the invasiveness of tumor cel s.
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Objective To investigate the clinical significance and abnormal expression of the CREB in different grade gliomas. Methods The expression of CREB was examined by using immunohistochemistry in brain tissues from the brain injury (5 cases) and different grade gliomas (55 cases).The mRNA and protein levels of CREB were further as?sessed using Western blot and RT-PCR in brain tissues from the patients with brain injury (10 cases) and those with dif?ferent grade gliomas (30 cases). Results The positive rates of CREB immunohistochemistry were 2/5 in control, 10/15 inⅠ-,Ⅱ11/12 in Ⅲ, 28/28 in Ⅳ. The positive rates of CREB were significantly different among different groups (H=28.183,P<0.05).The mRNA levels of CREB were 1.00 ± 0.000 in control, 1.35 ± 0.068 inⅠ-Ⅱ, 2.88 ± 0.111 in Ⅲand 3.75 ± 0.196 in Ⅳ. The expression of CREB was higher in the glioma than in control group, and the mRNA levels of CREB were significantly different among different groups(F=1.208,P<0.05). The protein levels of CREB were 0.311 ± 0.014 in control, 0.469±0.026 inⅠ-Ⅱ, 0.641±0.028 inⅢand 0.896±0.024 inⅣ. The protein levels of CREB were sig?nificantly different among different groups(F=1.123,P<0.05). Conclusion The expression of CREB is elevated in glio?mas with different differentiation degrees. The expression of CREB was positively correlated with the degree of differentia?tion, indicating that CREB may have an important regulatory role in the progress of gliomas.
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Objective To study the clinical effect of microsurgical surgery for the treatment of intracranial aneurysms in the acute phase. Methods 88 patients with intracranial aneurysm who were treated with the microscopic surgery in our hospital were selected as the research object. The prognosis was evaluated by Glasgow scale ( GOS) ,and the mortality rate during the follow-up period and postoperative complications were observed. Results All the patients received surgery success. The operation time was (60. 5 ± 20. 3) min,and the intraop-erative blood loss was (45. 2 ± 21. 5) mL. 12 months after operation,according to the GOS score of daily living ability,42 patients were of good prognosis and the other 46 cases were of poor prognosis. The good prognosis rate was 47. 7% and it is significantly higher than that of 3 months and 6 months after surgery. The difference was statistically significant (P<0. 05). There were 4 cases died among the 88 patients with a mortality of 4. 5%. Conclusion Using microsurgical treatment to treat intracranial aneurysms can receive good prognosis and low mortality rate. Complications were significantly improved after symptomatic treatment.