JS-K enhances renal cell carcinoma radiosensitivity through the Wnt/β-catenin signaling pathway and inhibits DNA damage repair.

The study investigated the effect of the glutathione S-transferase-activated nitric oxide donor JS-K [O2-(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate] to enhance the sensitivity of renal cancer cells to radiation therapy. JS-K has shown promising anti-tumor effects in various types of tumors; however, research on its role in cancer radioresistance is limited. The traditional concept is that renal cell carcinoma (RCC) has inherent resistance to radiation. Therefore, this study aimed to explore whether JS-K could enhance the sensitivity of renal cancer cells to radiation. The results showed that JS-K could effectively induce G2/M phase arrest, which is a crucial cell cycle phase that can lead to cell death. JS-K was also found to inhibit homologous recombination repair and the Wnt/β-catenin signaling pathway to enhance the radiosensitivity of renal cancer cells. In vivo experimentation utilizing animal models supported the function of JS-K in augmenting the radiosensitivity of renal cancer, and alterations in pertinent proteins were quantified by immunohistochemical analysis. The findings highlight the potential of JS-K as a promising radiosensitizer for treating RCC.