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Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Chitosan oligosaccharide suppresses osteosarcoma malignancy by inhibiting CEMIP via the PI3K/AKT/mTOR pathway
IlJin Sim1,2,3, WonGyom Choe3, JinJu Ri4
1Department of Orthopedics, The Second Affiliated Hospital of Zhejiang University School of Medicine, Jiefang Campus, 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.
Abstract:
Osteosarcoma is a malignant bone tumor that is prone to metastasize early and primarily affects children and adolescents. Cell migration-inducing protein (CEMIP) plays a crucial role in the progression and malignancy of various tumor diseases, including osteosarcoma. Chitosan oligosaccharide (COS), an oligomer isolated from chitin, has been found to have significant anti-tumor activity in various cancers. This study investigates the effects of COS on CEMIP expression in osteosarcoma and explores the underlying mechanism. In present study, in vitro experiments were conducted to confirm the inhibitory activity of COS on human osteosarcoma cells. Our results demonstrate that COS possesses inhibitory effects against human osteosarcoma cells and significantly suppresses CEMIP expression in vitro. Next, we studied the inhibition of the expression of CEMIP by COS and then performed bioinformatics analysis to explore the potential inhibitory mechanism of COS against signaling pathways involved in regulating CEMIP expression. Bioinformatics analysis predicted a close association between the PI3K signaling pathway and CEMIP expression and that the inhibitory effect of COS on CEMIP expression may be related to PI3K signaling pathway regulation. The results of this study show that COS treatment significantly inhibits CEMIP expression and the PI3K/AKT/mTOR signaling pathway, as observed both in vitro and in vivo. This study demonstrates that COS could inhibit the expression of CEMIP, which is closely related to osteosarcoma malignancy. This inhibitory effect may be attributed to the inhibition of the PI3K/AKT/mTOR signaling pathway in vitro and in vivo.
Insights
Chitosan oligosaccharide (COS) inhibits osteosarcoma cell growth and suppresses cell migration-inducing protein (CEMIP) expression. This effect is linked to the regulation of the PI3K/AKT/mTOR signaling pathway, offering a potential therapeutic strategy for osteosarcoma.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Osteosarcoma is a prevalent bone cancer in children and adolescents, characterized by early metastasis.
- Cell migration-inducing protein (CEMIP) is implicated in the progression and malignancy of osteosarcoma.
- Chitosan oligosaccharide (COS), derived from chitin, exhibits anti-tumor properties in various cancers.
Purpose of the Study:
- To investigate the effects of COS on CEMIP expression in osteosarcoma.
- To explore the underlying molecular mechanisms by which COS exerts its anti-tumor activity.
- To determine the role of the PI3K/AKT/mTOR signaling pathway in COS-mediated inhibition of osteosarcoma.
Main Methods:
- In vitro experiments were conducted using human osteosarcoma cells to assess the inhibitory activity of COS.
- CEMIP expression levels were measured following COS treatment.
- Bioinformatics analysis was employed to predict potential signaling pathways regulated by COS, focusing on those associated with CEMIP expression.
- In vivo studies were performed to validate the findings.
Main Results:
- COS demonstrated significant inhibitory effects on human osteosarcoma cell proliferation in vitro.
- COS treatment led to a notable suppression of CEMIP expression both in vitro and in vivo.
- Bioinformatics analysis and experimental results indicated that COS inhibits the PI3K/AKT/mTOR signaling pathway.
- The observed inhibition of CEMIP expression by COS is closely associated with the modulation of the PI3K/AKT/mTOR pathway.
Conclusions:
- COS exhibits significant anti-osteosarcoma activity by inhibiting cell proliferation and suppressing CEMIP expression.
- The anti-tumor effects of COS are mediated, at least in part, through the inhibition of the PI3K/AKT/mTOR signaling pathway.
- COS represents a promising therapeutic agent for osteosarcoma, warranting further investigation.
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