Effects Of Rab27a On Proliferation, Invasion, And Anti-apoptosis In Human Glioma Cell And Clinical Application In Glioma In Elderly Populations

Objective:This study aims to investigate the relationship between Rab27 a and the characteristics of glioma cell U251 such as proliferation, apoptosis, and invasion and to provide an experimental basis for future therapy in human glioma.Methods : Recombinant plasmid of pc DNA3.1-Rab27 a was constructed and transfected into U251 cells with the help of Lipofectamine?2000. The expression of Rab27 a was detected by Western blot. Cell viability, cell cycle, cell apoptosis, and cell migration were analyzed, respectively, by(3-(4,5)-dimethylthi-azol-2-yl)-2,5-diphenytetrazolium bromide(MTT) assay, flow cytometry, and Transwell invasion chamber methods. Meanwhile, the effect of Rab27 a on secretion of Cathepsin D in U251 cells was also examined. With the help of luciferase reporter assay system, the relationship between mi R-124 and gene Rab27 a expression was explored.Results: Western blot showed that the expression of Rab27 a was significantly increased in pc DNA3.1-Rab27 a transfection group(p<0.01) and that was significantly decreased in Rab27a-sh RNA transfection group(p<0.01) compared with control group. MTT assay, flow cytometry, and Transwell invasion chamber experiment indicated that cell viability(p<0.01), proliferation index(p<0.05), and invasion ability(p<0.01) were improved significantly in pc DNA3.1-Rab27 a transfection group compared with control group and that cell viability(p<0.01), proliferation index(p<0.05), and invasion ability(p<0.01) were reduced markedly in Rab27a-sh RNA transfection group compared with control group. The apoptosis analysis by flow cytometry demonstrated that the ratio of apoptosis in pc DNA3.1-Rab27 a transfection group was significantly lower than that in control group(p<0.05) and the ratio was notably higher in Rab27a-sh RNAtransfection group than that in the control group. Cathepsin D activity assay indicated that the release of Cathepsin D was enhanced inpc DNA3.1-Rab27 a transfection group compared to that in the control group(p<0.05).Conclusions: Rab27 a could increase the glioma cell ability, promote proliferation and invasion, and suppress cell apoptosis. The above-stated effects of Rab27 a possibly were exerted by increasing the secretion of Cathepsin D and regulated by mi R-124. In addition, the inhibition of expression of Rab27 a perhaps benefited the therapy for glioma patients.Objective: To evaluate the response to predictable chemotherapy according to Rab27 a expression pattern and the efficacy, toxicity and survival in patients with elderly gliomas.Methods:Chemotherapy patients(age ≥65years) of the treatment group which have Rab27 a expression were treated with temozolomide at a dose of 150~200 mg/m2 per day for 5 consecutive days of a 28-day cycle until they developed disease progression. No radiation therapy was administered. The endpoints included response rates, duration of response, median overall survival(OS), progression-free survival(PFS) and toxicity. The patients of control group which no expression of Rab27 a were not accept chemotherapy.Results: There are 32 patients(median age, 70 years; median Karnofsky performance status, 70) experienced a median OS of 7.4 months and a median PFS of 6.1months in treatment group. Of 29 patients who were assessed for response, 9 patients(31%) achieved a partial response, 12 patients(41%) maintained stable disease, and 8 patients(28%) developed progressive disease. In all, 160 cycles of temozolomide treatment were administered(median,4 cycles). Adverse events primarily were mild(such as nausea, emesis, fatigue, constipation and hematologic), with NCI CTC Grade 3 ~ 4 thrombocytopenia and neutropenia reported to occur in 6.25% and 9.38% of patients, respectively. No neurotoxicity was observed. Twenty-one patients experienced a median OS of 5.7 months and a median PFS of 4.0months in control group.Conclusions: The predictive chemotherapy according to Rab27 a expression in patientswith elderly gliomas could improve overall response rate with acceptable side-effect and thus worth for flirter investigation. However, whether the suvival time of the patients who have Rab27 a expression were prolonged need further research to confirm.