• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3751-3755
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• 2013

Backgroud and Aims: MicroRNA-206 has proven to be down-regulated in many human malignancies in correlation with tumour progression. Our study aimed to characterize miR-206 contributions to initiation and malignant progression of human osteosarcoma. Methods: MiR-206 expression was detected in human osteosarcoma cell 1ine MG63, human normal osteoblastic cell line hFOB 1.19, and paired osteosarcoma and normal adjacent tissues from 65 patients using quantitative RT-PCR. Relationships of miR-206 levels to clinicopathological characteristics were also investigated. Moreover, miR-206 mimics and negative control siRNA were transfected into MG63 cells to observe effects on cell viability, apoptosis, invasion and migration. Results: We found that miR-206 was down-regulated in the osteosarcoma cell line MG63 and primary tumor samples, and decreased miR-206 expression was significantly associated with advanced clinical stage, T classification, metastasis and poor histological differentiation. Additionally, transfection of miR-206 mimics could reduce MG-63 cell viability, promote cell apoptosis, and inhibit cell invasion and migration. Conclusions: These findings indicate that miR-206 may have a key role in osteosarcoma pathogenesis and development. It could serve as a useful biomarker for prediction of osteosarcoma progression, and provide a potential target for gene therapy.

• Genomics & Informatics
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• 제12권4호
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• pp.247-253
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• 2014

Osteosarcoma is the most common primary bone tumor, generally affecting young people. While the etiology of osteosarcoma has been largely unknown, recent studies have suggested that cyclooxygenase-2 (COX-2) plays a critical role in the proliferation, migration, and invasion of osteosarcoma cells. To understand the mechanism of action of COX-2 in the pathogenesis of osteosarcoma, we compared gene expression patterns between three stable COX-2-overexpressing cell lines and three control cell lines derived from U2OS human osteosarcoma cells. The data showed that 56 genes were upregulated, whereas 20 genes were downregulated, in COX-2-overexpressed cell lines, with an average fold-change > 1.5. Among the upregulated genes, COL1A1, COL5A2, FBN1, HOXD10, RUNX2, and TRAPPC2 are involved in bone and skeletal system development, while DDR2, RAC2, RUNX2, and TSPAN31 are involved in the positive regulation of cell proliferation. Among the downregulated genes, HIST1H1D, HIST1H2AI, HIST1H3H, and HIST1H4C are involved in nucleosome assembly and DNA packaging. These results may provide useful information to elucidate the molecular mechanism of the COX-2-mediated malignant phenotype in osteosarcoma.

• Asian Pacific Journal of Cancer Prevention
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• 제14권6호
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• pp.3681-3684
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• 2013

Deregulated miRNAs participate in osteosarcoma genesis. In this study, the expression of miRNA-218 in human osteosarcomas, adjacent normal tissues and Saos-2 human osteosarcoma cells was first assessed. Then the precise role of miRNA-218 in osteosarcoma cells was investigated. Upon transfection with a miR-218 expression vector, the proliferation of Saos-2 human osteosarcoma cells determined using the ATPlite assay was significantly suppressed, whilw migration of Saos-2 cells detected by wound healing and invasion determined using transwells were dramatically inhibited. Potential target genes of miR-218 were predicted and T-cell lymphoma invasion and metastasis 1 (TIAM1) and matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were identified. This was confirmed by western blotting, which showed that miR-218 expression inhibited TIAM1, MMP2 and MMP9 protein expression. Collectively, these data suggest that miR-218 acts as a tumor suppressor in osteosarcomas by down-regulating TIAM1, MMP2 and MMP9 expression.

• Molecules and Cells
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• 제38권5호
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• pp.432-440
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• 2015

Human osteosarcoma usually presented a high tendency to metastatic spread and caused poor outcomes, however, the underlying mechanism was still largely unknown. In the present study, using a series of in vitro experiments and an animal model, we investigated the roles of HOX antisense intergenic RNA (HOTAIR) during the proliferation and invasion of osteosarcoma. According with our results, HOTAIR was commonly overexpressed in osteosarcoma, which significantly correlated with advanced tumor stage, highly histological grade and poor prognosis. In vitro and in vivo experiments demonstrated that knockdown of HOTAIR could notably suppress cellular proliferation, inhibit invasion and decrease the secretion of MMP2 and MMP9 in osteosarcoma. Collectively, our results suggested that HOTAIR might be a potent therapeutic target for osteosarcoma.

• 한국미생물·생명공학회지
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• 제21권6호
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• pp.628-634
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• 1993

The inhibitory effects of various extracts from Chinese pepper on the mutagenicity and the growth of MG-63 human osteosarcoma cells were studied. Chinese pepper was extracted with methanol and then the methanol extract was further fractionated by using hexane, chloroform, ethyl acetate and butanol. The methanol extract of Chinese pepper revealed the strong antimutagenic activity on the aflatoxin B1(AFB1) and N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Ames mutagenicity test and SOS chromotest.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3103-3107
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• 2012

Osteosarcoma, the most common primary mesenchymal malignant tumor, usually has bad prognosis in man, with cancer stem-like cells (CSCs) considered to play a critical role in tumorigenesis and drug-resistance. It is known that phosphatidylinositol 3-kinase (PI3K) is involved in regulation of tumor cell fates, such as proliferation, cell cycling, survival and apoptosis. Whether and how PI3K and inhibitors might cooperate in human osteosarcoma CSCs is still unknown. We therefore evaluated the effects of LY294002, a PI3K inhibitor, on the cell cycle and apoptosis of osteosarcoma CSCs in vitro. LY294002 prevented phosphorylation of protein kinase B (PKB/Akt) by inhibition of PI3K phosphorylation activity, thereby inducing G0/G1 cell cycle arrest and apoptosis in osteosarcoma CSCs. Further studies also demonstrated that apoptosis induction by LY294002 is accompanied by activation of caspase-9, caspase-3 and PARP, which are involved in the mitochondrial apoptosis pathway. Therefore, our results indicate PI3K inhibitors may represent a potential strategy for managing human osteosarcoma via affecting CSCs.

• 한국식품영양과학회지
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• 제24권2호
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• pp.305-312
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• 1995

Ixeris dentata was extracted with methanol and then the methanol extract was further fractionated to hexane, chloroform, ethyl acetate, butanol and aqueous fraction. The methanol extract of lxeris dentata had the strong antimutagenic effect on the aflatoxin B1(AFB1) and N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) in Ames mutagenicity test and SOS chromotest. Among the solvent extracted fractions from the methanol extract, the chloroform fraction exhibited the greatest antimutagenic effect suppressing the mutagenicity of AFB1 with inhibition rate of 74 percent. The methanol extract of Ixeris dentata also revealed the inhibitory effect on the growth of MG-63 human osteosarcoma cells after 6 days of breeding at 37℃. The chloroform fraction and the ethyl acetate fraction from the methanol extract of lxeris dentata were most effective and inhibited the growth of MG-63 cells by 97 and 93 percent, respectively. It is suggested that the inhibitory effects of lxeris dentata on the mutagenicity and the growth of MG-63 human osteosarcoma cells are strong in the lipid soluble fractions.

• Clinical and Experimental Pediatrics
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• 제59권9호
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• pp.374-380
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• 2016

Purpose: Patients with unresectable, relapsed, or refractory osteosarcoma need a novel therapeutic agent. Metformin is a biguanide derivative used in the treatment of type II diabetes, and is recently gaining attention in cancer research. Methods: We evaluated the effect of metformin against human osteosarcoma. Four osteosarcoma cell lines (KHOS/NP, HOS, MG-63, U-2 OS) were treated with metformin and cell proliferation was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell cycle progression and apoptosis were evaluated using flow cytometric analysis, and migration and wound healing assay were performed. Fourteen female Balb/c-nude mice received KHOS/NP cell grafts in their thigh, and were allowed access to metformin containing water (2 mg/mL) ad libitum. Tumor volume was measured every 3-4 days for a period of 4 weeks. Results: Metformin had a significant antiproliferative effect on human osteosarcoma cells. In particular, metformin inhibited the proliferation and migration of KHOS/NP cells by activation of AMP-activated protein kinase and consequent inhibition of the mammalian target of rapamycin pathway. It also inhibited the proliferation of cisplatin-resistant KHOS/NP clone cells. Analysis of KHOS/NP xenograft Balb/c-nude models indicated that metformin displayed potent in vivo antitumor effects. Conclusion: Further studies are necessary to explore metformin's therapeutic potential and the possibilities for its use as an adjuvant agent for osteosarcoma.

• Toxicological Research
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• 제18권3호
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• pp.259-265
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• 2002

Resveratrol, a phytoalexin found in grapes, berries, and peanuts, is one of the most promising agents for cancer prevention. Recent studies show that the antitumor activity of resveratrol occurs through p53-mediated apoptosis. This study demonstrated the mechanism that resveratrol induced apoptosis in human osteosarcoma Saos-2 cells lacking p53. Treatment of osteosarcoma Saos-2 cells with resveratrol resulted in decrease of cell viability, which was revealed as apoptosis characterized by activation of caspase-3 protease as well as cleavage of poly(ADP-ribose) polymerase (PARP) with change of mitochondrial membrane potential transition. These results suggest that resveratrol may be potentially useful to treat osteosarcoma via activation of caspase protease and mitochondrial dysfunction.

• Fisheries and Aquatic Sciences
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• 제15권1호
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• pp.29-36
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• 2012

Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastasis. The mechanisms underlying osteosarcoma metastasis remain to be elucidated. Recently, anti-inflammatory agents were shown to be useful in the treatment of tumor progression. We previously isolated a natural anti-inflammatory peptide from the seahorse Hippocampus kuda bleeler. Here, we examined the antitumor metastatic activity of this peptide and investigated its mechanism. The peptide significantly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced invasive migration of human osteosarcoma MG-63 cells. Its inhibitory effect on invasive migration was associated with reduced expression of matrix metalloproteinases (MMP1 and MMP2). In addition, TPA stimulation increased intracellular reactive oxygen species (ROS) generation and small GTPase Rac1 expression, whereas the peptide decreased ROS generation and Rac1 activation. Taken together, these results suggest that the peptide inhibits invasive migration of MG-63 osteosarcoma cells by inhibiting MMP1 and MMP2 expression through downregulation of Rac1-ROS signaling.