2. Academic Validation
  3. Baicalin enhances the efficacy of 5-Fluorouracil in gastric cancer by promoting ROS-mediated ferroptosis

Baicalin enhances the efficacy of 5-Fluorouracil in gastric cancer by promoting ROS-mediated ferroptosis

  • Biomed Pharmacother. 2023 Jun 7;164:114986. doi: 10.1016/j.biopha.2023.114986.
Jingwen Yuan 1,  Shahid Ullah Khan 2,  Junfeng Yan 1,  Jiatong Lu 1,  Chen Yang 1,  Qiang Tong 3
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan 430060, China.
  • 2 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.
  • 3 Department of Gastrointestinal Surgery I Section, Renmin Hospital of Wuhan University, Wuhan 430060, China. Electronic address: [email protected].
PMID: 37295251 DOI: 10.1016/j.biopha.2023.114986
Abstract

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.

Keywords

5-Fluorouracil; Baicalin; Drug resistance; Ferroptosis; Gastric cancer.

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