Transcriptomic analysis of vitamin D3 (cholecalciferol)-mediated attenuation of cisplatin sensitivity in gastric cancer cells in vitro

 Ke Chen, Yu Pan

Abstract:

Cisplatin remains a cornerstone of chemotherapy for gastric cancer, but acquired resistance frequently limits its therapeutic efficacy. Vitamin D3/cholecalciferol (VD3) is widely used as a nutritional supplement; however, its influence on cisplatin responsiveness in gastric cancer cells remains unclear. In this study, gastric cancer cell lines were treated with cisplatin in the presence or absence of VD3, and cell viability, apoptosis, reactive oxygen species (ROS) accumulation, DNA damage-associated signaling, and transcriptomic changes were evaluated. VD3 significantly attenuated cisplatin-induced cytotoxicity in AGS, HGC-27, and MKN-45 cells. Co-treatment with VD3 reduced cisplatin-induced apoptosis, ROS accumulation, PARP cleavage, and γH2AX activation. Transcriptomic analysis showed that VD3 markedly reduced the number of cisplatin-responsive differentially expressed genes and altered gene programs associated with extracellular matrix organization, steroid metabolism, DNA damage response, and ABC transporter-related pathways. These findings suggest that VD3 exposure can attenuate cisplatin-induced cellular responses in gastric cancer cells and modulate transcriptional programs associated with cisplatin treatment. Given that the study was performed under in vitro conditions, further investigations are required to determine the underlying mechanisms and the potential clinical relevance of these observations.