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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.
AuthorsYang Zhou, Liang Bo Zhu, Ai Fen Peng, Tao Fang Wang, Xin Hua Long, Song Gao, Rong Ping Zhou, Zhi Li Liu
JournalMolecular medicine reports (Mol Med Rep) Vol. 11 Issue 2 Pg. 1352-7 (Feb 2015) ISSN: 1791-3004 [Electronic] Greece
PMID25351625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chromones
  • Enzyme Inhibitors
  • Morpholines
  • RNA, Messenger
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Fatty Acid Synthases
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
Topics
  • Bone Neoplasms (metabolism, pathology)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Cell Proliferation (drug effects)
  • Chromones (pharmacology)
  • Down-Regulation (drug effects)
  • Enzyme Inhibitors (pharmacology)
  • Fatty Acid Synthases (genetics, metabolism)
  • Humans
  • Morpholines (pharmacology)
  • Osteosarcoma (metabolism, pathology)
  • Phenotype
  • Phosphatidylinositol 3-Kinase (metabolism)
  • Proto-Oncogene Proteins c-akt (metabolism)
  • RNA, Messenger (metabolism)
  • Signal Transduction (drug effects)

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