Photosensitizer DTP Co-Administered with Statins Potentiates Renal Carcinoma Therapy by Modulating Cholesterol to Enhance PDT.

Renal cell carcinoma (RCC) is the most common histological subtype of kidney cancer. Although targeted therapies and immune checkpoint inhibitors have markedly improved patient outcomes, their efficacy remains limited. In recent years, photodynamic therapy (PDT) has drawn increasing attention for its role in cancer treatment. To investigate the effects of the novel porphyrin-based photosensitizer meso-5-[ρ-DTPA-aminophenyl]-10,15,20 triphenylporphyrin (DTP) on RCC, we employed the human renal tubular epithelial cell line HK-2, human RCC cell lines 786-O, ACHN, and A498, as well as the murine renal carcinoma cell line Renca. We assessed intracellular DTP uptake, phototoxicity, and subcellular localization, and further explored potential mechanisms through next-generation sequencing. Our results showed that DTP uptake was significantly higher in RCC cells than in normal renal tubular epithelial cells, and DTP-PDT exerted pronounced phototoxic effects on RCC cells. Through sequencing and in vitro analyses, we found that DTP-PDT markedly reduced cholesterol levels in RCC cells while inducing compensatory upregulation of HMGCR. In vivo experiments further demonstrated that combining DTP-PDT with statins produced stronger anticancer effects. Overall, this study provides compelling evidence that DTP-PDT exhibits potent cytotoxic activity against renal cell carcinoma, and that statins can further enhance its therapeutic efficacy.