Unveiling osteosarcoma responses to DAPT combined with cisplatin by using confocal Raman microscopy

Area of Science:

• Biomedical Engineering
• Molecular Oncology
• Chemical Biology

Background:

• Osteosarcoma (OS) is a primary bone malignancy with limited treatment options.
• Understanding drug interactions at a molecular level is crucial for developing effective cancer therapies.
• Confocal Raman microspectral imaging (CRMI) offers label-free, high-resolution analysis of cellular composition.

Purpose of the Study:

• To investigate the dose- and time-dependent effects of a γ-secretase inhibitor (DAPT) combined with cisplatin on osteosarcoma cells.
• To evaluate the synergistic interaction between DAPT and cisplatin using advanced imaging techniques.
• To elucidate the molecular mechanisms underlying the combined drug action on cellular composition and morphology.

Main Methods:

• Confocal Raman microspectral imaging (CRMI) for label-free cellular analysis.
• Principal Component Analysis-Linear Discriminant Analysis (PCA-LDA) for spectral data interpretation.
• K-means clustering and univariate imaging for visualizing subcellular changes.

Main Results:

• Combined DAPT and cisplatin treatment demonstrated a synergistic effect on osteosarcoma cells, distinct from cisplatin alone.
• Significant intracellular compositional changes were observed, indicating enhanced drug efficacy.
• Increased DAPT dosage and cisplatin treatment time promoted nuclear division and altered organelle morphology in OS cells.

Conclusions:

• The combination of DAPT and cisplatin exhibits a synergistic effect on osteosarcoma cells, impacting key cellular processes.
• CRMI technology effectively visualizes molecular and morphological changes induced by combined drug treatment.
• These findings provide a molecular basis for developing targeted and individualized treatment strategies for osteosarcoma.