Lobaplatin suppresses proliferation and peritoneal metastasis of colorectal cancer in a preclinical model.

Abstract

Peritoneal metastasis from colorectal cancer (CRC) is related to poor prognosis. Intraperitoneal chemotherapy is an efficient method to treat peritoneal metastasis (PM); however, the outcomes remain unsatisfactory. The present study aimed to investigate the antitumor activity of lobaplatin and its role in intraperitoneal chemotherapy. The findings showed that the proliferation of CRC was inhibited in a dose-dependent manner when DLD1 and HCT116 cells were treated with various concentrations of lobaplatin (0, 6.3, 12.5, 25, 50, and 100 μg/mL, respectively). Flow cytometry and Western blot analysis confirmed that lobaplatin affected CRC cells by inducing apoptosis and modulating the caspase family. In the animal study, nude mice were injected with DLD1 cells and divided into three groups. Lobaplatin was injected intraperitoneally to simulate intraperitoneal chemotherapy. Group A was the control group treated with PBS. Group B was injected with DLD1 and treated with lobaplatin simultaneously, while group C was treated with lobaplatin 1 week after cell injection. The results showed that group A harbored maximal tumors on the peritoneal surface, while group B had the least number (9.2 ± 1.3 and 0.4 ± 0.5, respectively P < 0.01). These findings indicated that lobaplatin suppressed the tumor growth as an intraperitoneal chemotherapy agent and achieved a satisfactory therapeutic effect at an early stage. Further blood test and tissue staining did not reveal any liver and kidney toxicity that was induced by lobaplatin. In conclusion, lobaplatin could be an effective and safe agent for CRC treatment, thereby commissioning a novel strategy in intraperitoneal chemotherapy for patients with peritoneal metastasis.

• Authors: Lina Shan, Bingjun Bai, Yiming Lv, Binbin Xie, Xuefeng Huang, Hongbo Zhu
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 108 Pg. 486-491 (Dec 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 30243080 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Cyclobutanes
• Organoplatinum Compounds
• Caspases
• lobaplatin

Topics

• Animals
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Cyclobutanes (pharmacology)
• Female
• HCT116 Cells
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Organoplatinum Compounds (pharmacology)
• Peritoneal Neoplasms (drug therapy, metabolism)
• Peritoneum (drug effects, metabolism)