Expression And Role Of PPAR-γ In Meningiomas And Troglitazone Induces Meningiomas Cell Apoptosis In Vitro

Background Meningioma is an intracranial benign tumor with high incidence.Operation is the main treatment method,but the radiation therapy and nonsurgical treatment method are the important subsidiary methods. Therefore,to investigate the new therapeutic targets is the core of treatment method.PPAR-γis a nuclear transcription factor that is related to insulin glycoregulatory activity and adipocyte differentiation.In addition to improve insulin resistance,immunoregulation and anti-inflammatory effect,its ligands also affect anti-tumor activity and resistance to terminal differentiation and significantly inhibited to invasion and metastasis of tumors cells.It is rarely reported on the researches of PPAR-γand its activator-troglitazone in the investigations of meningiomas.Our research explores the expression and role of PPAR-γin meningiomas and that troglitazone induce in Vitro meningiomas cell apoptosis by means of RT-PCR and immunohistochemistry.This dissertation consists of two parts:ⅠThe mRNA and protein expression of PPAR-γin meningiomasObjective To investigate the mRNA and protein expression of PPAR-γin meningiomas.Methods To research on the surgical specimens of meningiomas by means of RT-PCR and immunohistochemistry:Total DNA were extracted through guanidine thiocyanate method and were reversely transcripted into cDNA,then amplified by PCR.The products underwent electrophoresis,then observed by proliferating cell nuclear antigen as examination index. Paraffin-embedded tissues were cut into serial sections and stained according to SP means.The products wer observed by double-blind method..Results Atypical group((?)=0.465±0.375) were higher than benign group((?)= 0.766±0.481,t=7.56,P＜0.01);female expression is slightly higher than men(t=5.68,P＜0.05).Immunohistochemistry results showed that all atypical specimens expressed higher protein level of PPAR-γcompared with benign(P＜0.05),and between PPAR-γprotein expression in patients with meningioma and age and sex,there were no significant correlation(P＞0.05). Conclusions Significant deference was found in PPAR-γindices of benign tumors and atypical tumors,and the expression of PPAR-γwas positively correlated with its proliferative activity.ⅡExperiment on meningomas cells in VitroObjective To investigate the antitumor effect of PPAR-γto meningioma cells. Methods 16 meningioma specimens were choosen to in vitro primary cell culture(Ⅰgrade,benign,10 cases;Ⅱgradel,atypical type,6 cases),the role of troglitazone in the growth of meningioma cells were detected by the application of MTT method,the apoptosis of meningioma cells which were interverned by troglitazone were detected through the method of flow cytometry.Results MTT test shows that OD values of the experimental groups were significantly lower than the control group,troglitazone can promote apoptosis(or death) and this effect is closely related with the concentration,that is,the greater the drug concentration,the smaller the value of its OD.Concentration of 1μmol/L of troglitazone on cultured cells transfected meningioma no significant effect on growth;troglitazone of 10 or 50μmol/L for 24 hours lower than the control OD value(P＜0.05),and it is most notably a 72-hour inhibition(P＜0.01),after 120 hours the inhibitory effect become weaken.The test results showed that the meningioma cells by different concentrations of 24h,48h,72h,120h results in different rates of apoptosis between the experimental group and the control group,there was significant differences(P＜0.05);the time between the groups and between different time groups were significantly different(P＜0.05).Troglitazone can induce apoptosis of meningioma cells,the apoptosis rate has a positive correlation with the concentration and acting time;but underwent after 72h by 50,100μmol/L,the death of cells significantly increased.Conclusions Our research shows that concentration of 10 or 50μmol/L of troglitazone can not only inhibit meningioma cells growth but also induce cells apoptosis 24 hours after treated,and 72-hour inhibition most notably a(P＜0.01),after 120 hours the inhibitory effect become weakened.In vitro,the impact on meningioma cells growth and apoptosis of troglitazone is a concentration-dependent.