title: Inhibitory effects of forkhead box L1 gene on osteosarcoma growth through the induction of cell cycle arrest and apoptosis.
abstract: Forkhead box L1 (FOXL1), which is considered a novel candidate tumor suppressor, inhibits proliferation and invasion in certain types of cancer. However, the regulation and function of FOXL1 in osteosarcoma remains unclear. The expression of FOXL1 gene in osteosarcoma tissues and cell lines was examined using RT-PCR, immunohistochemistry and western blot analysis. pcDNA-FOXL1 carrying full-length FOXL1 cDNA was constructed to upregulate the level of FOXL1 expression in osteosarcoma cell lines. The proliferation, cell cycle and apoptosis of osteosarcoma cells in vitro or in vivo were examined following transfection with pcDNA-FOXL1. In addition, the expression of p21, p27, cytochrome c and caspase-3, which may be involved in the regulation of the cell cycle and apoptosis was examined using western blot analysis. The results showed that FOXL1 expression was downregulated in osteosarcoma tissues and cell lines. Loss or downregulation of FOXL1 was associated with poor prognosis. Ectopic FOXL1 expression inhibited cell proliferation in vitro and in vivo. The ectopic FOXL1 expression increased the expression of p21 and p27, which induced G1 arrest in the U-2 OS cells. In addition, the ectopic FOXL1 expression induced cytochrome c release between mitochondria and cytoplasm, which disrupted the mitochondrial transmembrane potential and triggered intrinsic pathway apoptosis. In conclusion, the downregulation of FOXL1 expression was associated with osteosarcoma cell growth. Restoration of FOXL1 gene expression by gene therapy may have a therapeutic potential for patients with osteosarcoma.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Xinshe
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000473:pathology; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology
chemical_list: C491001:FOXL1 protein, human; D051858:Forkhead Transcription Factors