Refined Baohe formula protects against 5-fluorouracil-induced intestinal mucositis by modulating AKT pathway in CT-26 tumor-bearing mice

• Main Authors: Liya Liu (Author), Youqin Chen (Author), Ying Cheng (Author), Meizhu Wu (Author), Jie Li (Author), Jiapeng Li (Author), Thomas Joseph Sferra (Author), Senthilkumar Sankararaman (Author), Jianfeng Chu (Author), Aling Shen (Author), Jun Peng (Author)
• Format: Book
• Published: Elsevier, 2023-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Background: 5-Fluorouracil (5-FU) is one of the most commonly prescribed anticancer agents. However, intestinal mucositis is a well-known adverse event, which limits its therapeutic use. Refined Baohe formula (RBF) is derived from Baohe Pills with a potent gastrointestinal protective effect. However, the effects of RBF on 5-FU-induced intestinal mucositis remain unknown. Thus, this study investigated the effects and mechanism of RBF on 5-FU-induced intestinal mucositis in a CT-26 xenograft mice colorectal cancer (CRC) model. Methods: The composition of the RBF preparation was analyzed by high-pressure liquid chromatography. CT-26 cells bearing mice were intraperitoneally administered 150 mg/kg of 5-FU on day 1 to construct a 5-FU-induced intestinal injury model. Mice in the 5-FU + RBF group were intragastrically administrated with RBF (12.4 g/kg) for 4 days. Tumor volume and weight were determined, body weight and diarrhea scores were monitored, leukocytes were calculated, and hematoxylin-eosin staining, immunohistochemistry, and terminal deoxynucleotidyl transferase dUTP nick end labeling were performed to investigate the therapeutic efficiency and underlying mechanisms of RBF on 5-FU-induced intestinal mucositis mice. Results: RBF didn`t affect the effect of tumor suppression, while attenuated diarrhea associated with 5-FU-induced intestinal mucositis and significantly reduced leucocyte toxicity. Additionally, RBF significantly promoted cell proliferation and inhibited cell apoptosis, and up-regulated CDK4, c-Myc, and B-cell lymphoma-2 expression, while down-regulated Bax expression, as well as enhanced both p-AKT and AKT expression in intestinal crypts of 5-FU-treated mice. Conclusions: RBF attenuated 5-FU-induced intestinal mucositis by inhibiting apoptosis and promoting cell proliferation by modulating the AKT pathway and its downstream effectors in a CT-26 xenograft mouse CRC model.

Item Description

2667-1425
10.1016/j.prmcm.2023.100230