Xianglian pill combined with 5-fluorouracil enhances antitumor activity and reduces gastrointestinal toxicity in gastric cancer by activating the p38 MAPK/NF-κB signaling pathway

Ethnopharmacological relevance Perioperative or postoperative adjuvant chemotherapy based on 5-fluorouracil (5-FU) is a common first-line adjuvant therapy for gastric cancer (GC). However, drug resistance and the side effects of 5-FU have reduced its efficacy. Among these side effects, gastrointestinal (GI) toxicity is one of the most common. Xianglian Pill (XLP) is a Chinese patent medicine that is commonly used for the treatment of diarrhoea. It may have a protective effect on the intestinal mucosa and a reduction in inflammation. Recent studies have shown that many components of XLP can have an inhibitory effect on the growth of tumor cells. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear. Aim of the study To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity. Materials and methods XLP was administered orally during intraperitoneal injection of 5-FU in GC mice model. Mice were continuously monitored for diarrhea and xenograft tumor growth. After 2 weeks, the mice were sacrificed and serum was collected to determine interleukin-6 levels. The expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) was determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined. Results The results showed that XLP could alleviate GI mucosal injury caused by 5-FU, alleviated diarrhea, and inhibited the expression of nuclear factor (NF)-κB and myeloid differentiation primary response-88. Besides, XLP could promote the 5-FU-induced apoptosis of GC cells and enhance the inhibitory effect of 5-FU on tumor xenografts. Further study showed that XLP administration could regulate the expression of p38 MAPK. Xenograft tumor. Conclusions XLP in combination with 5-FU could alleviate its GI side effects and enhance its inhibitory effect on xenograft tumor. Moreover, these effects were found to be related to the regulation of the p38 MAPK/NF-κB pathway.