Expression of LASS2 Can be Regulated by Dihydroartemisinin to Regulate Cisplatin Chemosensitivity in Bladder Cancer...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Bladder cancer remains a significant health concern with limited treatment options.
• Cisplatin chemotherapy is a standard treatment but faces challenges with resistance and efficacy.
• Identifying novel therapeutic strategies to augment cisplatin efficacy is crucial.

Purpose of the Study:

• To investigate dihydroartemisinin's potential to enhance cisplatin chemotherapy efficacy.
• To explore the role of LASS2 (also known as CERS2) in this interaction.
• To determine if dihydroartemisinin modulates LASS2 expression.

Main Methods:

• Bioinformatic analysis of databases (TCMSP, CTR-DB, TCGA-BLC) to identify LASS2 as a dihydroartemisinin target.
• In vitro cell experiments to assess synergistic effects of cisplatin (DDP) and dihydroartemisinin (DHA).
• In vivo animal studies to evaluate tumor growth inhibition.
• Western blot, real-time PCR, and immunohistochemical analysis to measure LASS2 expression.

Main Results:

• LASS2 expression is significantly different in bladder cancer tissues compared to normal tissues and correlates with cisplatin chemosensitivity.
• High LASS2 expression is associated with better overall survival and less advanced disease.
• Dihydroartemisinin demonstrated a strong binding affinity to LASS2 and effectively upregulated its expression in bladder cancer cells and in vivo.
• The combination of DHA and DDP showed synergistic effects and inhibited tumor growth in mice.

Conclusions:

• Dihydroartemisinin upregulates LASS2 (CERS2) expression in bladder cancer.
• This upregulation enhances cisplatin chemosensitivity, suggesting a novel therapeutic approach.
• The DHA-LASS2 interaction presents a promising strategy for improving bladder cancer treatment outcomes.