title: LY294002 inhibits the malignant phenotype of osteosarcoma cells by modulating the phosphatidylinositol 3‑kinase/Akt/fatty acid synthase signaling pathway in vitro.
abstract: Increasing evidence suggests that fatty acid synthase (FASN) is crucial in the carcinogenesis of various types of tumor. In addition, the phosphatidylinositol 3‑kinase (PI3K)/Akt signaling pathway, which is closely associated with cellular metabolism, affects cancer biology. However, whether the malignant phenotype of osteosarcoma (OS) cells is regulated by the PI3K/Akt/FASN signaling pathway and how the PI3K family specific inhibitor, 2‑(4‑morpholinyl)‑8‑phenyl‑chromone (LY294002) affects the malignant phenotype of OS cells remains to be elucidated. In the present study, U2‑OS and MG‑63 cells were treated with LY294002 and subsequently western blot analysis was used to examine Akt, p‑Akt and FASN protein expression. Additionally, FASN mRNA was detected by reverse transcription quantitative polymerase chain reaction. MTT and fluorescence‑activated cell sorting assays were used to assess proliferation and apoptosis. Migration and invasion were investigated using wound healing and transwell invasion assays. The results demonstrated that LY294002 suppressed the PI3K/Akt/FASN signaling pathway. However, the malignant phenotypes of OS cells mentioned above were significantly inhibited. The present results indicated that LY294002 inhibits the malignant phenotype of OS cells via modulation of the PI3K/Akt/FASN signaling pathway in vitro and may be a new therapeutic strategy for the management of OS.
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Liang Bo
authors.initials: LB
authors.lastname: Zhu
authors.affiliation: College of Humanities, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ai Fen
authors.initials: AF
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Tao Fang
authors.initials: TF
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xin Hua
authors.initials: XH
authors.lastname: Long
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Rong Ping
authors.initials: RP
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Zhi Li
authors.initials: ZL
authors.lastname: Liu
mesh_terms: D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D012333:RNA, Messenger; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D064429:Fatty Acid Synthases; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt