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

Abstract

The aim of this study was to clarify the dose- and time-dependent effect of the γ-secretase inhibitor (DAPT) combined with cisplatin on osteosarcoma (OS) cells, evaluated by confocal Raman microspectral imaging (CRMI) technology. The intracellular composition significantly changed after combined drug action compared with the sole cisplatin treatment, proving the synergistic effect of DAPT combined with cisplatin on OS cells. The principal component analysis-linear discriminant analysis revealed the main compositional variations by distinguishing spectral characteristics. K-means cluster and univariate imaging were used to visualize the changes in subcellular morphology and biochemical distribution. The results showed that the increase of the DAPT dose and cisplatin treatment time in the combination treatment induced the division of the nucleus in OS cells, and other organelles also showed significant physiological changes compared with the effect of sole cisplatin treatment. After understanding the cellular response to the combined drug treatment at a molecular level, the achieved results provide an experimental fact for developing suitable individualized tumor treatment protocols.