title: Delivery of inhibitor of growth 4 (ING4) gene significantly inhibits proliferation and invasion and promotes apoptosis of human osteosarcoma cells.
abstract: Growing evidence has suggested that inhibitor of growth 4 (ING4), a novel member of ING family proteins, plays a critical role in the development and progression of different tumors via multiple pathways. However, the function of ING4 in human osteosarcoma remains unclear. To understand its potential roles and mechanisms in inhibiting osteosarcoma, we constructed an expression vector pEGFP-ING4 and transfected the human osteosarcoma cells using this vector. We then studied the effects of over-expressed ING4 in the transfected cells on the proliferation, apoptosis and invasion of the osteosarcoma cells. The up-regulation of ING4 in the osteosarcoma cells, arising from the stable pEGFP-ING4 gene transfection, was found to significantly inhibit the cell proliferation by the cell cycle alteration with S phase reduction and G0/G1 phase arrest, induce cell apoptosis via the activation of the mitochondria pathway, and suppress cell invasion through the down-regulation of the matrix metalloproteinase 2 (MMP-2) and MMP-9 expression. In addition, increased ING4 level evoked the blockade of NF-κB signaling pathway and down-regulation of its target proteins. Our work suggests that ING4 can suppress osteosarcoma progression through signaling pathways such as mitochondria pathway and NF-κB signaling pathway and ING4 gene therapy is a promising approach to treating osteosarcoma.
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman OK 73019, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Medical Research, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xia
authors.affiliation: Department of Orthopedics, Guangdong Key Lab of Orthopaedic Technology and Implant, Guangzhou General Hospital of Guangzhou Military Command, 111 Liuhua Road, Guangzhou 510010, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman OK 73019, USA.
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Mao
mesh_terms: D017209:Apoptosis; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; C483230:ING4 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9