title: RAS Promotes Proliferation and Resistances to Apoptosis in Meningioma.
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 μmol/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 μmol/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 IOMM-Lee cells after FTS (75 μmol/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 of p-ERK and p-Akt decreased significantly in 75 mg/kg group and 100 mg/kg group when compared with the control group and 50 mg/kg group (all P < 0.05). Our findings provide strong evidence that RAS protein is highly expressed in meningioma cells, and the RAS activity is inhibited by downregulating ERK and AKT signal pathway, which may further inhibit the growth of meningioma.
authors.affiliation: Department of Radiation Oncology, Nanchang University, Nanchang, 330006, China.|Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, 330029, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410000, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Song
authors.affiliation: Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, 330029, China.
authors.forename: Jingao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, 330029, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Ao
authors.affiliation: Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, 330029, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Military University, No 440 North Chengdu Road, Huangpu District, Shanghai, 200003, China.
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Military University, No 440 North Chengdu Road, Huangpu District, Shanghai, 200003, China.
authors.forename: Chenran
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Liangyu
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Military University, No 440 North Chengdu Road, Huangpu District, Shanghai, 200003, China. hh_hehua@sina.com.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial Maternal and Child Health Hospital, No 318 Bayi Avenue, Nanchang, 330006, China. ouping_huang@126.com.
authors.forename: Ouping
authors.initials: O
authors.lastname: Huang
mesh_terms: D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004311:Double-Blind Method; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D008579:Meningioma / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D011897:Random Allocation; D012459:Salicylates / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
chemical_list: D000970:Antineoplastic Agents; D012459:Salicylates; C093323:farnesylthiosalicylic acid; D005204:Farnesol; D018631:ras Proteins
keywords: AKT protein; ERK protein; IOMM-LEE; Meningioma; RAS protein