title: LY294002 suppresses the malignant phenotype and sensitizes osteosarcoma cells to pirarubicin chemotherapy.
abstract: Pirarubicin is frequently used in chemotherapy against tumors. However, clinical use is severely limited by the development of progressive dose-dependent cardiomyopathy and acquired drug resistance. LY294002 is a commonly used pharmacologic inhibitor, which selectively inhibits the phosphoinositide 3-kinase-AKT nexus. The aim of this study was to investigate the combined inhibitory effect of LY294002 and pirarubicin on human osteosarcoma (OS) cells in vitro. The inhibitory effect of LY294002 plus pirarubicin on U2-OS and MG-63 OS cell proliferation, apoptosis, migration and invasion was investigated by cell proliferation, wound healing and Transwell invasion assays. The results revealed that LY294002 and pirarubicin synergistically induced apoptosis, and inhibited the growth, migration and invasion of OS cells. This indicates that LY294002 enhanced the effects of pirarubicin on OS in vitro. LY294002 combined with pirarubicin may thus be a future therapeutic strategy in OS.
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: Graduate School of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Zhen Hao
authors.initials: ZH
authors.lastname: Zhong
authors.affiliation: 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: Liang Bo
authors.initials: LB
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Guo Mei
authors.initials: GM
authors.lastname: Zhang
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: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D004317:Doxorubicin; C027260:pirarubicin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt