MARK2 enhances cisplatin resistance via PI3K/AKT/NF-κB signaling pathway in osteosarcoma cells

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Osteosarcoma is the most common primary bone cancer in children and young adults.
• Cisplatin resistance is a significant challenge, leading to poor prognosis and inadequate treatment outcomes.
• Identifying novel biomarkers and mechanisms of chemoresistance is crucial for improving osteosarcoma patient survival.

Purpose of the Study:

• To investigate the role of microtubule-affinity regulating kinase 2 (MARK2) in osteosarcoma cisplatin resistance.
• To explore the underlying molecular mechanisms by which MARK2 influences chemoresistance.
• To evaluate MARK2 as a potential therapeutic target and predictive biomarker for osteosarcoma.

Main Methods:

• Analysis of Gene Expression Omnibus datasets to correlate MARK2 expression with prognosis and chemoresistance.
• Quantitative analysis of MARK2 expression in osteosarcoma cells versus normal cells.
• In vitro and in vivo experiments involving MARK2 overexpression and inhibition to assess effects on cisplatin resistance.

Main Results:

• High MARK2 expression was associated with poor prognosis and positively correlated with chemoresistance in osteosarcoma.
• MARK2 was significantly upregulated in osteosarcoma cells compared to normal cells.
• MARK2 overexpression promoted cisplatin resistance, while inhibition suppressed it, both in vitro and in vivo.

Conclusions:

• MARK2 overexpression enhances cisplatin resistance in osteosarcoma by increasing P-glycoprotein expression and reducing apoptosis via PI3K/AKT/NF-κB pathway activation.
• MARK2 serves as a potential therapeutic target for overcoming cisplatin resistance.
• MARK2 is a promising biomarker for predicting cisplatin resistance in osteosarcoma patients.