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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.
Introduction:
Chemotherapy resistance is one of the main reasons for osteosarcoma (OS) relapses. Understanding the regulatory mechanisms of cisplatin resistance is critical for developing potential therapeutic strategies for OS. This study aimed to examine the role of VSIG2 in OS chemotherapy resistance.
Methods:
Cell viability assay, colony formation assay, LDH cytotoxicity assay, and a subcutaneous xenograft model were used to explore VSIG2's role in OS cisplatin resistance in vitro and in vivo. A luciferase reporter assay was carried out to determine the pathways regulated by VSIG2. Co-Immunoprecipitation was carried out to investigate the interaction of VSIG2.
Results:
VSIG2 is upregulated in OS tissues with poor response to neoadjuvant chemotherapy. Functionally, VSIG2 promoted cisplatin resistance determined by cell models and animal models. Mechanistically, VSIG2 activated the PI3K/AKT pathway. Moreover, VSIG2 interacted with mTOR and increased p70 S6 Kinase phosphorylation. Furthermore, inhibition of mTOR significantly reversed the effect of VSIG2 on cisplatin resistance.
Discussion:
Our findings emphasize the key role of VSIG2 in chemoresistance of OS, deepening the understanding of the molecular mechanisms of OS chemoresistance generation.
Conclusion:
In summary, our findings suggested that VSIG2 may confer novel platinum resistance via activating the PI3K/AKT/mTOR pathway, providing a potential target for OS therapy.
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