文献类型：期刊文献

英文题名：Baicalin enhances the chemotherapy sensitivity of oxaliplatin-resistant gastric cancer cells by activating p53-mediated ferroptosis

作者：Shao, Lihua[1,2,3];Zhu, Li[4];Su, Rong[2];Yang, Chunting[2];Gao, Xiaqing[2];Xu, Yan[2];Wang, Hongwei[1];Guo, Chenglong[1,5];Li, Hailong[1,2,3]

第一作者：Shao, Lihua

通信作者：Li, HL[1];Li, HL[2];Li, HL[3]

机构：[1]Gansu Univ Chinese Med, Affiliated Hosp, Dept Geriatr, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Chinese Med, Sch Clin Med 1, Dept Internal Med, 35 East Dingxi Rd, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Chinese Med, Key Lab Gansu Prov Prescript Min & Innovat Transla, Lanzhou 730000, Gansu, Peoples R China;[4]Hubei Minzu Univ, Emergency Dept, Minda Hosp, Enshi 445000, Hubei, Peoples R China;[5]Gansu Univ Chinese Med, Affiliated Hosp, Dept Osteoporosis, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学第二附属医院

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Affiliated Hosp, Dept Geriatr, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Sch Clin Med 1, Dept Internal Med, 35 East Dingxi Rd, Lanzhou 730000, Gansu, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Key Lab Gansu Prov Prescript Min & Innovat Transla, Lanzhou 730000, Gansu, Peoples R China.|[10735]甘肃中医药大学;[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;

年份：2024

卷号：14

期号：1

外文期刊名：SCIENTIFIC REPORTS

收录：;Scopus(收录号：2-s2.0-85192739926);WOS:【SCI-EXPANDED(收录号:WOS:001218726300041)】；

基金：No Statement Available

语种：英文

外文关键词：Gastric cancer; Multidrug resistance; Baicalin; Ferroptosis; p53 suppressor gene

摘要：Gastric cancer is one of the most common malignant tumors, and chemotherapy is the main treatment for advanced gastric cancer. However, chemotherapy resistance leads to treatment failure and poor prognosis in patients with gastric cancer. Multidrug resistance (MDR) is a major challenge that needs to be overcome in chemotherapy. According to recent research, ferroptosis activation is crucial for tumor therapeutic strategies. In this work, we explored the solution to chemoresistance in gastric cancer by investigating the effects of the Chinese medicine monomer baicalin on ferroptosis. Baicalin with different concentrations was used to treat the parent HGC27 and drug-resistant HGC27/L cells of gastric cancer. Cell viability was measured by CCK8, and synergistic effects of baicalin combined with oxaliplatin were evaluated using Synergy Finder software. The effects of baicalin on organelles and cell morphology were investigated using projective electron microscopy. Iron concentration, MDA production and GSH inhibition rate were measured by colorimetry. ROS accumulation was detected by flow cytometry. The ferroptosis-related genes (IREB2, TfR, GPX4, FTH1), P53, and SLC7A11 were analysed by Western blot, and the expression differences of the above proteins between pretreatment and pretreatment of different concentrations of baicalin, were assayed in both parental HGC27 cells and Oxaliplatin-resistant HGC27/L cells. Mechanically, Baicalin disrupted iron homeostasis and inhibits antioxidant defense, resulting in iron accumulation, lipid peroxide aggregation, and specifically targeted and activated ferroptosis by upregulating the expression of tumor suppressor gene p53, thereby activating the SLC7A11/GPX4/ROS pathway mediated by it. Baicalin activates ferroptosis through multiple pathways and targets, thereby inhibiting the viability of oxaliplatin-resistant gastric cancer HGC27/L cells and enhancing the sensitivity to oxaliplatin chemotherapy.