title: Potentiation of the antitumor activity of adriamycin against osteosarcoma by cannabinoid WIN-55,212-2.
abstract: Osteosarcoma is the most frequent primary malignant bone tumor that occurs in children and adolescents. The present study aimed to identify novel therapeutic strategies for osteosarcoma, by assessing the antitumor activity of the cannabinoid WIN-55,212-2 and its combined effect with adriamycin (ADM) against the MG-63 human osteosarcoma cell line. To evaluate the antiproliferative action of these molecules, a Cell Counting kit-8 (CCK-8) assay was used. The ability of cannabinoid to inhibit the migration, invasion and angiogenic activity of MG-63 cells were assessed by scratch, Transwell® chamber and angiogenesis assays, respectively,in vitro. To examine the alterations in expression of targeted genes, quantitative polymerase chain reaction and western blot analysis were used. The administration of cannabinoid combined with ADM was demonstrated to inhibit the growth of MG-63 cells, resulting in a cell viability of 32.12±3.13%, which was significantly lower (P<0.05) compared with the cell viability following treatment with cannabinoid (70.86±7.55%) and ADM (62.87±5.98%) alone. Greater antimetastasis and antiangiogenic activities were also observed following the coadministration of the two agents compared with individual treatments and controls. In addition, the expression levels of Notch-1, matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in MG-63 cells were downregulated following the treatments with cannabinoid alone or in combination with ADM. In conclusion, the present findings demonstrated that cannabinoid WIN-55,212-2 may significantly potentiate the antiproliferative, antimetastasis and antiangiogenic effects of ADM against MG-63 cells via the downregulation of Notch-1, MMP-2 and VEGF. These findings may offer a novel strategy for the treatment of osteosarcoma.
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Niu
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Medical Records, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Chang-Yan
authors.initials: CY
authors.lastname: Xu
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sha
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Gui-Bin
authors.initials: GB
authors.lastname: Bi
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.affiliation: Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Tian-Hong
authors.initials: TH
authors.lastname: Nie
keywords: WIN-55,212-2; adriamycin; cannabinoid; combination; osteosarcoma