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Published on: May 3, 2021
VSIG2 Promotes Osteosarcoma Cisplatin Resistance Via Activating PI3K/AKT/mTOR Pathway
Xueren Zhong1, Jing Xiang2, Xiaoyu Yang1
1Department of Spinal Surgery, Yuebei People's Hospital Affiliated to Shantou University Medical College, Shaoguan, China.
Vesicle-associated membrane protein A (VAMP) 2 homolog 2 (VSIG2) promotes cisplatin resistance in osteosarcoma (OS). VSIG2 activates the PI3K/AKT/mTOR pathway, offering a potential therapeutic target for overcoming OS chemoresistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chemotherapy resistance is a major cause of osteosarcoma (OS) relapse.
- Understanding cisplatin resistance mechanisms is crucial for effective OS therapeutic strategies.
Purpose of the Study:
- To investigate the role of VSIG2 in mediating chemoresistance in osteosarcoma.
- To elucidate the molecular pathways involved in VSIG2-driven cisplatin resistance.
Main Methods:
- In vitro and in vivo experiments including cell viability, colony formation, and xenograft assays.
- Luciferase reporter assays to identify regulated pathways.
- Co-immunoprecipitation to determine protein interactions.
Main Results:
- VSIG2 is upregulated in OS tissues resistant to neoadjuvant chemotherapy.
- VSIG2 overexpression confers cisplatin resistance in both cellular and animal models.
- VSIG2 activates the PI3K/AKT/mTOR pathway, leading to increased p70 S6 Kinase phosphorylation.
- Inhibition of mTOR reverses VSIG2-mediated cisplatin resistance.
Conclusions:
- VSIG2 plays a significant role in osteosarcoma chemoresistance.
- VSIG2 confers platinum resistance by activating the PI3K/AKT/mTOR pathway.
- VSIG2 represents a potential therapeutic target for overcoming chemoresistance in OS.
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