Chengdu University of Traditional Chinese Medicine, Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization of Chinese Herbal Medicine of MOE, Chengdu, 610075, China.
School of Pharmacy, West China School of Pharmacy, Sichuan University, Chengdu, 610075, China.
J Ethnopharmacol. 2024 May 23;326:117988. doi: 10.1016/j.jep.2024.117988. Epub 2024 Feb 28.
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 can reduce inflammation and has a protective effect on the intestinal mucosa. Recent studies have shown that many components of XLP can inhibite tumor cell growth. However, the therapeutic effect of XLP in combination with 5-FU on GC is unclear.
To investigate whether the combination of XLP and 5-FU can enhance anti-GC activity while reducing GI toxicity.
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. Pathological changes, the expression of pro-inflammatory factors and p38 mitogen-activated protein kinase (MAPK) in GI tissue were determined by Western blot analysis. Pathological changes, apoptosis levels and p38 MAPK expression levels in xenograft tissues were also determined.
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.
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.
基于 5-氟尿嘧啶（5-FU）的围手术期或术后辅助化疗是胃癌（GC）的常见一线辅助治疗方法。然而，药物耐药性和 5-FU 的副作用降低了其疗效。在这些副作用中，胃肠道（GI）毒性是最常见的一种。香连丸（XLP）是一种常用于治疗腹泻的中药。它可以减轻炎症，对肠黏膜有保护作用。最近的研究表明，XLP 的许多成分可以抑制肿瘤细胞生长。然而，XLP 与 5-FU 联合治疗 GC 的疗效尚不清楚。
研究 XLP 与 5-FU 联合应用是否能增强抗 GC 活性，同时降低 GI 毒性。
在 GC 小鼠模型中，XLP 通过腹腔注射 5-FU 进行口服给药。连续监测小鼠腹泻和异种移植肿瘤生长情况。2 周后，处死小鼠并采集血清，测定白细胞介素-6 水平。通过 Western blot 分析测定 GI 组织中促炎因子和 p38 丝裂原活化蛋白激酶（MAPK）的表达变化。还测定了异种组织中的病理变化、凋亡水平和 p38 MAPK 表达水平。
结果表明，XLP 能减轻 5-FU 引起的 GI 黏膜损伤，缓解腹泻，抑制核因子（NF）-κB 和髓样分化原初反应-88 的表达。此外，XLP 能促进 5-FU 诱导的 GC 细胞凋亡，增强 5-FU 对肿瘤异种移植的抑制作用。进一步研究表明，XLP 给药可调节 p38 MAPK 的表达。
XLP 联合 5-FU 可减轻其 GI 副作用，并增强其对异种移植瘤的抑制作用。此外，这些作用与调节 p38 MAPK/NF-κB 通路有关。
