Sulfasalazine Sensitizes Polyhematoporphyrin-Mediated Photodynamic Therapy in Cholangiocarcinoma by Targeting xCT

Abstract

Cholangiocarcinoma (CCA), which is highly malignant, shows a relatively poor prognosis, due to the insensitivity of the tumour to chemotherapy and radiotherapy. Photodynamic therapy (PDT) has become a promising palliative therapeutic option for patients with unresectable cholangiocarcinoma (CCA), while the functional amount of ROS is limited by intracellular redox systemen. Sulfasalazine (SASP), a well-known anti-inflammatory agent, which also acts as an inhibitor of the amino acid transport system xc (xCT), decreases the intracellular glutathione (GSH) level, thus weakening the antioxidant defence of the cell by inhibition of the antiporter. However, the combination of SASP and PDT remains unexplored. We have reported that polyhematoporphyrin (PHP)-mediated PDT inhibits the cell viability of CCA cells and organoids. Furthermore, in PHP-enriched HCCC-9810 and TFK-1CCA cells, SASP enhances the sensitivity to PHP-mediated PDT through a GSH-dependent mechanism. We found that PHP-PDT can up-regulate xCT expression to promote cells against overloaded ROS, while SASP reduces GSH levels. After the combination of SASP and PHP-PDT, cell viability and GSH levels were significantly inhibited. xCT was also observed to be inhibited by SASP in human organoid samples. Our findings suggest that, in combination with PDT, SASP has potential as a promising approach against CCA.

Comprehensive Analysis of the Potential Immune-Related Biomarker ATG101 that Regulates Apoptosis of Cholangiocarcinoma Cells After Photodynamic Therapy

“…In our previous microarray data ( Tan et al, 2019 ; Zheng et al, 2021 ), it was found that many tumors including CHOL and colorectal cancer, up-regulated ATG101 after PDT treatment. The current view believes that the main anti-tumor effect of PDT is to induce cell apoptosis.…”

Folic Acid–Modified Long-Circulating Liposomes Loaded with Sulfasalazine For Targeted Induction of Ferroptosis in Melanoma

“…SSZ has been shown to inhibit cell viability by inducing intracellular ROS production . Therefore, we used DCFH-DA to assess the ROS levels in the B16F10 cells.…”

“…SSZ has been shown to inhibit cell viability by inducing intracellular ROS production. 40 Therefore, we used DCFH-DA to assess the ROS levels in the B16F10 cells. ROS generation was significantly increased in FA-SSZ-Lips-treated B16F10 cells compared with that in SSZ treatment alone (Figure 6C).…”

Photodynamic Therapy Combined with Ferroptosis Is a Synergistic Antitumor Therapy Strategy

“…In another study exploring PHP-PDT against cholangiocarcinoma, it was found that PHP-PDT could up-regulate the expression of xCT in cholangiocarcinoma cells. After combined SASP, it can play a synergistic effect by reducing the level of GSH and increasing the content of ROS [184]. Based on the above studies, we believe that SASP may cooperate with PDT to promote ferroptosis by reducing the expression of xCT, but more research is needed to explore the specific mechanism of the combined therapy.…”