PAR1 Is a Candidate Target for the Treatment of Peritoneal Dissemination in Gastric Cancer

Graph showing the IC₅₀ of PTX under different conditions of treatment of MKN45/PAR1 cells with different SCH79797 concentrations for 72 h. SD values are shown on the lines showing PTX (black line), PTX plus 30 nM SCH79797 (gray line), PTX plus 70 nM SCH79797 (light blue line), and PTX and 150 nM SCH79797 (dotted line). IC₅₀: 50% Inhibitory concentration; PTX: paclitaxel; PAR1: protease-activated receptor-1; SD: standard deviation.

Assessment of peritoneal dissemination of MKN45/PAR1 cells in mice. An MKN45/PAR1 cell-bearing mouse is depicted in the images on the left. This mouse had bloody ascites with a number of peritoneal disseminations found in the abdominal cavity. The images on the right show a MKN45/mock cell-bearing mouse. This mouse had no ascites, and a few peritoneal disseminations were found in the abdominal cavity. PCI scores for both groups are shown under the figure; the difference between groups is significant (p<0.001). The graph on the right-hand side shows the difference in tumor weights between the two mouse groups, which is also significant (p<0.001). PAR1: protease-activated receptor-1; PCI: Peritoneal Cancer Index.

Assessment of the tumor shrinkage effect of each drug on the peritoneal dissemination of MKN45/PAR1 cells. Representative images of MKN45/PAR1 cell-bearing mice are shown in the upper panel. The drug intraperitoneally administered is shown above the image for each group with the mean PCI score presented immediately below. The graphs of PCI score and tumor weights presented in the bottom panel shows the p-values for the means of each group compared with the PBS group as the reference. PCI: Peritoneal Cancer Index; PBS: phosphate buffered saline; PTX: paclitaxel; PAR1: protease-activated receptor-1.

Assessment of body weight change over time in each group. Body weight and weight gain of the mice inoculated with MKN45/PAR1 cells into the stomach wall were monitored over a period of 28 days after inoculation. Data are mean±standard deviation, n=5 per group, with the p-value compared with non-inoculated mice as the control at the end of experimental period. White squares indicate the body weight of mice with no inoculated MKN45/PAR1 cells as the control; black squares indicate the body weights of mice treated with PBS after inoculation with MKN45/PAR1 cells; solid black triangles indicate the body weights of mice treated with 70 nM SCH79797 after inoculation with MKN45/PAR1 cells; white triangles indicate the body weights of mice treated with PTX after inoculation with MKN45/PAR1 cells; and black rhombuses indicate the body weights of mice treated with PTX and 70 nM SCH79797 after inoculation with MKN45/PAR1 cells. *p=0.002; **p=0.013; ***p=0.038; ****p=0.155. PBS: phosphate buffered saline; PTX: paclitaxel; PAR1: protease-activated receptor-1.