Background: Peritoneal lavage after cancer surgery is performed to reduce microscopic residual tumors in the peritoneum. This study evaluated the effects and mechanism of dialysate lavage in reducing the peritoneal implantation of gastric cancer cells.
Methods: Gastric cancer cells (MKN45 or AGS) were cultured with 1.5% peritoneal dialysate (PD) or normal saline (NS) for 30 min. The in vitro cell susceptibility to dialysate, including cell proliferation, cell death, cleaved PARP expression, and mitochondrial membrane potential, was evaluated. A murine model for gastric cancer cell peritoneal seeding was established to test the effects of PD and NS lavage on animal survival and tumor growth.
Results: A significant decrease in cell proliferation in PD and NS (75.2 ± 0.1 vs. 12.4 ± 0.2% in MKN45, p = 0.009; 58.2 ± 0.01 vs. 28.0 ± 0.01% in AGS, p = 0.008), an increase in mitochondrial permeability transition (93.0 ± 2.6 vs. 18.0 ± 2.9% in MKN45, p = 0.021; 86.8 ± 4.6 vs. 47.7 ± 10.2% in AGS, p < 0.001), and an increase in the expression of cleaved PARP and increased death (25.6 ± 9.4 vs. 16.9 ± 5.3% in MKN45, p = 0.031; 39.5 ± 5.1 vs. 20.9 ± 3.9% in AGS, p = 0.008) were recorded for gastric cancer cells separately exposed to PD and NS. Twenty-four days after inoculating MKN45 cells (5 × 10(6)/0.1 ml) in the peritoneal cavity, the average number of seeded tumors was 67.3 ± 10.8, 92.3 ± 6.0, and 29.2 ± 16.7 (p = 0.032), and the total weight of tumors was 0.98 ± 0.21, 0.58 ± 0.12, and 0.31 ± 0.17 g (p = 0.008), respectively, for mice receiving sham operation, NS lavage, and PD lavage. The 45-day survival rate for the PD lavage group was 22% compared to 0% for the sham injection and NS lavage groups (p = 0.034).
Conclusion: PD induced significant cytotoxicity in gastric cancer cells that was related to mitochondrial perturbation. The use of PD lavage was effective in reducing the peritoneal implantation of gastric cancers in a murine model.
2015 S. Karger AG, Basel.