Experimental study on the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil to treat PDX model of pseudomyxoma peritonei

Abstract

Objective To evaluate the efficacy and toxicity of intraperitoneal injection of 5-fluorouracil (5-Fu) in patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP). Methods One PMP tumor from surgery was used to establish PMP PDX models, which were equally randomized into control (no treatment), vehicle (normal saline, 0.2 ml) and treatment (5-Fu, 50 mg/kg, 0.2 ml) groups. Experimental peritoneal cancer index (ePCI) score, body weight, and pathological examination were performed to evaluate the efficacy and toxicity. Results PDX models replicating human PMP were established and diagnosed as high grade mucinous carcinoma peritonei with signet ring cells. Average ePCI score of treatment group was significantly lower than control and vehicle groups [(0.9±1.2) points vs. (3.6±1.7) points vs. (2.7±1.1) points, F=9.253, P<0.01]. Histopathological study revealed obvious tumor necrosis and reduced signet ring cells in the treatment group. The Ki-67 label index of treatment group was significantly lower than control group and vehicle group [(57.3±15.1)% vs. (72.2±15.1)% vs. (70.0±14.0)%, F=4.923, P<0.05]. The body weight of treatment group was significantly lower than control group and vehicle group [(19.7±2.8) g vs. (22.7±1.8) g vs. (21.9±1.7) g, F=4.654, P<0.05]. Major toxicities in the treatment group were animal death (10.0%), congestive splenomegaly (88.9%), lymphocyte accumulation (77.8%), bile canaliculus hyperplasia and obstruction (22.2%), cholestasis (100.0%), and acidophilic body (55.6%) in the liver. Conclusion In the PDX model of human PMP, intraperitoneal injection of 5-Fu could inhibit tumor proliferation and progression, with lowered ePCI score and reduced Ki-67, and toxicity was mainly on liver. Key words: Pseudomyxoma peritonei; PDX model; 5-Fluorouracil; Intraperitoneal injection; Organ toxicity