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

Autor: Yu L; 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., Qin JY; 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., Sun C; 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., Peng F; School of Pharmacy, West China School of Pharmacy, Sichuan University, Chengdu, 610075, China. Electronic address: fujing126@yeah.net., Chen Y; 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., Wang SJ; 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., Tang J; 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., Lin ZW; 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., Wu LJ; 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., Li J; 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., Cao XY; 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., Li WQ; 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., Xie XF; 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. Electronic address: xxf14544@163.com., Peng C; 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. Electronic address: cdtcmpengcheng@126.com.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 May 23; Vol. 326, pp. 117988. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1016/j.jep.2024.117988
Abstrakt: 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 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.
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. 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.
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.
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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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