시스플라틴이 CT26 cancer-bearing nude mouse에서 포토론을

Abstract

Photodynamic therapy is a non-invasive cancer treatment method that can selectively laser irradiation on cancer tissue after the injection of photosensitizer. However, photodynamic therapy is necessary to develop a method that can enhance the cancer treatment efficiency due to limitation the light transmission and the anticancer activity of photosensitizer. This study was carried out to investigate the changes of anti-tumor effect of cisplatin on photodynamic therapy (PDT) with photolon in nude mouse tumor bearing model. The nude mouse tumor bearing model was prepared by injecting cultured colon cancer cells (CT26 cells, 1x105 cells/mouse) into the back of KSN/Slc nude mice. The experimental group was divided into the control group, the cisplatin group (3 mg/kg BW), 80 J/cm2 group, cisplatin+80 J/cm2 group and laser 140 J/cm2 group. Cisplatin (3 mg/kg BW) and photolon (2.5 mg/kg BW) were injected into the abdominal cavity and after 2 hours, laser light(660 nm) was irradiated on the tumor mass and the volume of tumor mass was measured with time. After 24 hours of laser irradiation, RNA was isolated from tumor tissues and gene expression changes were observed by mRNA sequencing analysis. The tumor volume of the control group was increased by 133% at day 8 compared to day 0, and 118% by the cisplatin treated group. The tumor volume in the 80 J/cm2 group increased by 68% on day 8 compared to day 0, and increased by 7% on day 8 compared to day 0 in the Cis+80 J/cm2 group. Tumor volume of 140 J/cm2 group was reduced by 27% on day 8. After 1 day of PDT, the tumor tissues were excised, fixed into 10% paraformaldehyde, stained with hematoxylin-eosine(HE) and observed under a light microscope. Necrotic cells were not observed in the tumor tissue of the control group and cisplatin groups. In the 80 J/cm2 group, necrosis was partially observed in the tumor tissue, and in the Cis+80 J/cm2 group, necrotic cells were extensively observed in the tumor tissue. After 1 day of PDT, mRNA-seq analysis of the expression of the genes involved in the immune response in the control and 80 J/cm2 groups showed no difference. In Cis+80 J/cm2 group, expression of genes involved in immune response was increased compared to 80 J/cm2 group. After 1 day of PDT, the expression of chemotaxis-related 12 genes and immune response-related 18 genes were different in cancer tissues of 80 J/cm2 group and Cis+80 J/cm2 group. The combination of cisplatin and photolon-PDT significantly reduced tumor size and increased the expression of immune response-related genes in tumor tissues. These results suggest that the combination of cisplatin and PDT may be an effective method for enhancing cancer treatment.