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      Antitumor activity of dobutamine on human osteosarcoma cells

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          Abstract

          Dobutamine has been widely used for the treatment of heart failure and cardiogenic shock since the 1970s. Osteosarcoma is the most commonly observed malignant bone tumor in children. Currently, there are no effective drugs for the treatment of osteosarcoma. In the present study, the potential anticancer activity of dobutamine on human osteosarcoma cells was examined. Human osteosarcoma MG-63 cells were treated with dobutamine at various concentrations and for various incubation times. The inhibition of cell growth by dobutamine was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was utilized to evaluate the effect of dobutamine on cell apoptosis and the cell cycle. Furthermore, the expression levels of caspase-3 and caspase-9 were assessed by western blot analysis. The influence of dobutamine on cancer cell migration and invasion was additionally evaluated using wound-healing assay and the Boyden Chamber migration method. Dobutamine significantly inhibited the growth of MG-63 cells at a concentration of 10 µM or higher when incubated for 12 h or longer (P=0.023). Dobutamine augmented cell apoptosis and arrested the cell cycle in the G2/M phase. Western blot analysis revealed that dobutamine induces expression of caspase-3 and caspase-9. In addition, the invasiveness and migration of MG-63 cells was inhibited by dobutamine in a concentration-dependent manner. The results of the present study may lead to novel applications for dobutamine in the treatment of osteosarcoma.

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          Most cited references14

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          Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach.

          The heterogeneity and instability of human tumors hamper straightforward identification of cancer-causing mutations through genomic approaches alone. Herein we describe a mouse model of liver cancer initiated from progenitor cells harboring defined cancer-predisposing lesions. Genome-wide analyses of tumors in this mouse model and in human hepatocellular carcinomas revealed a recurrent amplification at mouse chromosome 9qA1, the syntenic region of human chromosome 11q22. Gene-expression analyses delineated cIAP1, a known inhibitor of apoptosis, and Yap, a transcription factor, as candidate oncogenes in the amplicon. In the genetic context of their amplification, both cIAP1 and Yap accelerated tumorigenesis and were required to sustain rapid growth of amplicon-containing tumors. Furthermore, cIAP1 and Yap cooperated to promote tumorigenesis. Our results establish a tractable model of liver cancer, identify two oncogenes that cooperate by virtue of their coamplification in the same genomic locus, and suggest an efficient strategy for the annotation of human cancer genes.
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            PML, YAP, and p73 are components of a proapoptotic autoregulatory feedback loop.

            p73 has been identified as a structural and functional homolog of the tumor suppressor p53. The transcriptional coactivator Yes-associated protein (YAP) has been demonstrated to interact with and to enhance p73-dependent apoptosis in response to DNA damage. Here, we show the existence of a proapoptotic autoregulatory feedback loop between p73, YAP, and the promyelocytic leukemia (PML) tumor suppressor gene. We demonstrate that PML is a direct transcriptional target of p73/YAP, and we show that PML transcriptional activation by p73/YAP is under the negative control of the proto-oncogenic Akt/PKB kinase. Importantly, we find that PML and YAP physically interact through their PVPVY and WW domains, respectively, causing PML-mediated sumoylation and stabilization of YAP. Hence, we determine a mechanistic pathway in response to DNA damage that could have relevant implications for the treatment of human cancer.
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              Current Therapeutic Strategies and Novel Approaches in Osteosarcoma

              Osteosarcoma is the most frequent malignant primary bone tumor and a main cause of cancer-related death in children and adolescents. Although long-term survival in localized osteosarcoma has improved to about 60% during the 1960s and 1970s, long-term survival in both localized and metastatic osteosarcoma has stagnated in the past several decades. Thus, current conventional therapy consists of multi-agent chemotherapy, surgery and radiation, which is not fully adequate for osteosarcoma treatment. Innovative drugs and approaches are needed to further improve outcome in osteosarcoma patients. This review describes the current management of osteosarcoma as well as potential new therapies.

                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                June 2016
                20 April 2016
                20 April 2016
                : 11
                : 6
                : 3676-3680
                Affiliations
                [1 ]Department of Orthopedics, Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China
                [2 ]Department of Orthopedics, First People's Hospital of Yancheng, Yancheng, Jiangsu 224006, P.R. China
                [3 ]Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, P.R. China
                [4 ]School of Medicine, University of California, San Diego, CA 92103, USA
                [5 ]Tianjin Sunnypeak Biotech Co., Ltd., Tianjin 300457, P.R. China
                Author notes
                Correspondence to: Dr Qirong Dong, Department of Orthopedics, Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, P.R. China, E-mail: dqr_szu@ 123456163.com
                Dr Guolin Ma, Department of Radiology, China-Japan Friendship Hospital, 2 Yinghua Dongjie, Beijing 100029, P.R. China, E-mail: maguolin1007@ 123456qq.com
                Article
                OL-0-0-4479
                10.3892/ol.2016.4479
                4887865
                27284371
                5669751f-659c-4263-89d9-53445c56b500
                Copyright: © Yin et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 28 March 2015
                : 08 March 2016
                Categories
                Articles

                Oncology & Radiotherapy
                osteosarcoma,dobutamine,anticancer activity
                Oncology & Radiotherapy
                osteosarcoma, dobutamine, anticancer activity

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