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Web End = Mol Neurobiol (2017) 54:779787 DOI 10.1007/s12035-016-9763-z
http://crossmark.crossref.org/dialog/?doi=10.1007/s12035-016-9763-z&domain=pdf
Web End = RAS Promotes Proliferation and Resistances to Apoptosis in Meningioma
Chunling Jiang1,2 & Tao Song3 & Jingao Li2 & Fan Ao2 & Xiaochang Gong2 & Yicheng Lu4 &
Chenran Zhang4 & Liangyu Chen5 & Yunhui Liu5 & Hua He4 & Ouping Huang6
Received: 30 July 2015 /Accepted: 28 January 2016 /Published online: 28 March 2016 # Springer Science+Business Media New York 2016
Abstract In this study, we investigated the influence of elevated RAS expression on the growth of meningioma in vivo and in vitro. The IOMM-LEE cells, representing a cell line derived from malignant meningioma, were divided into blank control group (cells without any drug treatment), negative control group (cells treated with an equal volume of normal saline to replace drug), and farnesyl thiosalicylic acid (FTS)-treated group (cells treated with FTS). Methyl-thiazole-tetrazolium bromide (MTT) assay and flow cytometer (with cells after FTS
(75 mol/L) treatment for 48 h) were utilized to determine the proliferation and apoptosis, respectively, of IOMM-LEE cells after RAS inhibition. Western blot analysis was used for semi-quantitative analysis of p-ERK and p-AKT levels. Animal model of human meningioma was established with sub-renal capsule transplantation, and mice were divided into two groups: experimental group (50 mg/kg group, 75 mg/kg group, and 100 mg/kg, hypodermic injection with FTS) and control group. Proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry (IHC). Western blot analysis was used for detecting ERK and AKT signal pathway. The proliferation of IOMM-LEE cells decreased dramatically and apoptosis rate increased significantly in FTS-treated group compared to blank control group and negative control group (all P < 0.05). At FTS concentration of 75 mol/L, the apoptosis rate of IOMM-LEE cells reduced significantly over time (P < 0.05). Cell cycle analysis showed that IOMM-LEE cells exhibited G1-arrest in the FTS-treated group, compared to no cell-cycle arrest in blank control group and the negative control group (P < 0.05). Further, significantly decreased ERK and AKT phosphorylation levels were detected in IOMMLee cells after FTS (75 mol/L) treatment for 48 h, compared to blank control group and negative control group (P < 0.05). The results in vivo experiments showed that after FTS treatment, tumor volume, PCNA LI, and the levels...