Year-end Sale % OFF 
Abstract
Lung metastasis constitutes the leading cause of the death in patients with osteosarcoma. We have previously reported that plasminogen activator inhibitor-1 (PAI-1) regulates the invasion and lung metastasis of osteosarcoma cells in a mouse model and as well as in clinical samples. In the present study, we examined the anti-metastatic effect of SK-216, a small compound PAI-1 inhibitor, in human 143B osteosarcoma cells. An in vitro study showed that SK-216 treatment suppressed invasion activity by inhibiting PAI-1 expression in 143B cells, but had no influence on their proliferation or migration. 143B cells treated with SK-216 exhibited reduced matrix metalloproteinase-13 (MMP-13) secretion in a dose-dependent manner. Moreover, intraperitoneal injection of SK-216 into mouse models resulted in downregulation of PAI-1 expression levels in the primary tumors and showed suppression of lung metastases without influencing the proliferative activity of the tumor cells in the primary lesions. These results indicate that SK-216, a PAI-1 inhibitor, may serve as a novel drug to prevent lung metastasis in human osteosarcoma.
Highlights
Osteosarcoma is the most common primary bone tumor that primarily affects children and adolescents
The prognosis of patients with osteosarcoma has improved through the use of combination therapy such as adjuvant chemotherapy in conjunction with surgical wide resection [1], reported five-year survival rates for patients with lung metastasis remain at approximately 30% [2]
Inhibition of plasminogen activator inhibitor-1 (PAI-1) expression in 143B cells that were treated with SK-216 at 25 and 50 μM when inhibition of PAI-1 expression in 143B cells that were treated with SK-216 at 25 and 50 μM when compared with non-treated cells (Figure 1a, Supplementary Figure S1a)
Summary
Osteosarcoma is the most common primary bone tumor that primarily affects children and adolescents. The prognosis of patients with osteosarcoma has improved through the use of combination therapy such as adjuvant chemotherapy in conjunction with surgical wide resection [1], reported five-year survival rates for patients with lung metastasis remain at approximately 30% [2]. As lung metastases constitute the leading cause of death in patients with osteosarcoma, it is important to suppress lung metastases in osteosarcoma for improving their prognosis. Toward this end, our group previously reported that intravenous injection of miR-143 significantly suppressed the lung metastasis of human 143B osteosarcoma cells in a mouse model [3]. High levels of PAI-1 are widely reported to be positively correlated with poor clinical outcome in various cancers [6]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
