黄芩通过促进 ROS 介导的铁死亡增强 5-氟尿嘧啶在胃癌中的疗效。
Baicalin enhances the efficacy of 5-Fluorouracil in gastric cancer by promoting ROS-mediated ferroptosis.
机构信息
Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Integrative Science Center of Germplasm Creation in Western China (Chongqing) Science City and Southwest University, College of Agronomy and Biotechnology, Southwest University, Chongqing 400715, China; Department of Biochemistry, Women Medical and Dental College, Khyber Medical University, Abbottabad 22080, Pakistan.
出版信息
Biomed Pharmacother. 2023 Aug;164:114986. doi: 10.1016/j.biopha.2023.114986. Epub 2023 Jun 7.
BACKGROUND
5-Fluorouracil (5-Fu) is one of the most commonly used chemotherapy drugs for gastric cancer (GC). But the increase of drug resistance makes the prognosis of patients worse. Studies have shown that Baicalin can not only inhibit various cancers but also increase the sensitivity of cancers to chemotherapy. However, how Baicalin works in chemotherapeutic resistance of GC are unclear.
METHODS
CCK8 (Cell Counting Kit 8) was used to detect the IC50 (half maximal inhibitory concentration) of Baicalin and 5-Fu. Proliferation, migration, and invasion of GC were tested through colony formation assay and transwell assay. Fluorescent probes detected intracellular reactive oxygen species (ROS). RNA-seq (RNA sequencing) detected differentially expressed genes and pathways, and qPCR (Quantitative Real-time PCR) tested the expression of ferroptosis-related genes.
RESULTS
The combination of Baicalin and 5-Fu inhibited GC progression and increased intracellular ROS levels. Both the inhibition of malignant phenotype of gastric cancer cells and the generation of intracellular ROS caused by Baicalin could be saved by the inhibitor of ferroptosis-Ferrostatin-1 (Fer-1). Heat map of enriched differentially expressed genes identified by RNA-seq included four ferroptosis-related genes, and subsequent GO (Gene Ontology) analysis suggested an association between the ferroptosis pathway and Baicalin treatment. The changes in expression of ferroptosis-related genes were validated by qPCR, and the result confirmed that the combination of Baicalin and 5-Fu promoted ferroptosis in GC.
CONCLUSIONS
Baicalin inhibits GC and enhances 5-Fu by promoting ROS-related ferroptosis in GC.
背景
5-氟尿嘧啶（5-Fu）是胃癌（GC）最常用的化疗药物之一。但是，耐药性的增加使患者的预后恶化。研究表明，黄芩素不仅能抑制多种癌症，还能提高癌症对化疗的敏感性。然而，黄芩素在 GC 化疗耐药中的作用机制尚不清楚。
方法
用 CCK8（细胞计数试剂盒 8）检测黄芩素和 5-Fu 的 IC50（半抑制浓度）。通过集落形成实验和 Transwell 实验检测 GC 的增殖、迁移和侵袭。荧光探针检测细胞内活性氧（ROS）。RNA-seq（RNA 测序）检测差异表达基因和通路，qPCR（定量实时 PCR）检测铁死亡相关基因的表达。
结果
黄芩素与 5-Fu 联合抑制 GC 进展并增加细胞内 ROS 水平。黄芩素抑制胃癌细胞恶性表型和产生细胞内 ROS 均可被铁死亡抑制剂 Ferrostatin-1（Fer-1）挽救。RNA-seq 鉴定的差异表达基因热图包括四个铁死亡相关基因，随后的 GO（基因本体论）分析表明铁死亡通路与黄芩素治疗之间存在关联。qPCR 验证了铁死亡相关基因表达的变化，结果证实黄芩素与 5-Fu 联合促进了 GC 中的铁死亡。
结论
黄芩素通过促进 GC 中的 ROS 相关铁死亡来抑制 GC 并增强 5-Fu 的作用。
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