白藜芦醇通过靶向 MAPK 信号通路抑制鼻咽癌（NPC）。

Resveratrol Inhibits Nasopharyngeal Carcinoma (NPC) by Targeting the MAPK Signaling Pathway.

机构信息

Institute (College) of Integrated Medicine, Dalian Medical University, Dalian, P.R. China.

Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.

出版信息

Anticancer Agents Med Chem. 2024;24(16):1207-1219. doi: 10.2174/0118715206319761240705115109.

DOI:10.2174/0118715206319761240705115109

PMID:38988166

Abstract

BACKGROUND

With conventional cancer treatments facing limitations, interest in plant-derived natural products as potential alternatives is increasing. Although resveratrol has demonstrated antitumor effects in various cancers, its impact and mechanism on nasopharyngeal carcinoma remain unclear.

OBJECTIVE

This study aimed to systematically investigate the anti-cancer effects of resveratrol on nasopharyngeal carcinoma using a combination of experimental pharmacology, network pharmacology, and molecular docking approaches.

METHODS

CCK-8, scratch wound, and transwell assays were employed to confirm the inhibitory effect of resveratrol on the proliferation, migration, and invasion of nasopharyngeal carcinoma cells. H&E and TUNEL stainings were used to observe the morphological changes and apoptosis status of resveratrol-treated cells. The underlying mechanisms were elucidated using a network pharmacology approach. Immunohistochemistry and Western blotting were utilized to validate key signaling pathways.

RESULTS

Resveratrol inhibited the proliferation, invasion, and migration of nasopharyngeal carcinoma cells, ultimately inducing apoptosis in a time- and dose-dependent manner. Network pharmacology analysis revealed that resveratrol may exert its anti-nasopharyngeal carcinoma effect mainly through the MAPK pathway. Immunohistochemistry results from clinical cases showed MAPK signaling activation in nasopharyngeal carcinoma tissues compared to adjacent tissues. Western blotting validated the targeting effect of resveratrol, demonstrating significant inhibition of the MAPK signaling pathway. Furthermore, molecular docking supported its multi-target role with MAPK, TP53, PIK3CA, SRC, etc. Conclusion: Resveratrol has shown promising potential in inhibiting human nasopharyngeal carcinoma cells by primarily targeting the MAPK pathway. These findings position resveratrol as a potential therapeutic agent for nasopharyngeal carcinoma.

摘要

背景

随着传统癌症治疗方法面临局限，人们对植物源性天然产物作为潜在替代品的兴趣日益增加。虽然白藜芦醇在各种癌症中表现出抗肿瘤作用，但它对鼻咽癌的影响和机制尚不清楚。

目的

本研究旨在通过实验药理学、网络药理学和分子对接方法的综合应用，系统研究白藜芦醇对鼻咽癌的抗癌作用。

方法

采用 CCK-8、划痕实验和 Transwell 实验证实白藜芦醇对鼻咽癌细胞增殖、迁移和侵袭的抑制作用。H&E 和 TUNEL 染色观察白藜芦醇处理细胞的形态变化和凋亡状态。采用网络药理学方法阐明其潜在机制。免疫组化和 Western blot 用于验证关键信号通路。

结果

白藜芦醇抑制鼻咽癌细胞的增殖、侵袭和迁移，最终呈时间和剂量依赖性诱导细胞凋亡。网络药理学分析表明，白藜芦醇可能主要通过 MAPK 通路发挥其抗鼻咽癌作用。临床病例的免疫组化结果显示，与相邻组织相比，MAPK 信号在鼻咽癌组织中被激活。Western blot 验证了白藜芦醇对 MAPK 信号通路的靶向作用，显示出显著的抑制作用。此外，分子对接支持其与 MAPK、TP53、PIK3CA、SRC 等多靶点作用。