目的探究重链多肽亚基由铁蛋白重链多肽1(ferritin heavy chain polypeptide 1,FTH1)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达和临床意义。方法基于癌症基因图谱(The Cancer Genome Atlas,TCGA)数据...目的探究重链多肽亚基由铁蛋白重链多肽1(ferritin heavy chain polypeptide 1,FTH1)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达和临床意义。方法基于癌症基因图谱(The Cancer Genome Atlas,TCGA)数据库分析FTH1在HNSCC组织和癌旁组织中的差异表达情况,并分析其表达与肿瘤分期的关系和对总生存的影响。采用Cox比例风险模型评估影响HNSCC患者预后的因素。使用GSEA软件预测FTH1可能参与调控的信号通路。结果FTH1在HNSCC中高表达,且与肿瘤分期有关(均P<0.05)。FTH1高表达的HNSCC患者总生存率降低(P<0.05)。单因素Cox分析结果显示,高表达的FTH1和肿瘤分期均是影响HNSCC患者的预后因素(均P<0.05)。多因素Cox分析结果显示,肿瘤分期和性别均是影响HNSCC患者的预后因素(均P<0.05)。FTH1的通路富集分析显示,FTH1的高表达样本显著富集到溶酶体、谷胱甘肽代谢、磷酸戊糖途径及癌症通路等基因集。结论FTH1可作为HNSCC的临床预后标志物。展开更多
Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an acti...Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.展开更多
文摘目的探究重链多肽亚基由铁蛋白重链多肽1(ferritin heavy chain polypeptide 1,FTH1)在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的表达和临床意义。方法基于癌症基因图谱(The Cancer Genome Atlas,TCGA)数据库分析FTH1在HNSCC组织和癌旁组织中的差异表达情况,并分析其表达与肿瘤分期的关系和对总生存的影响。采用Cox比例风险模型评估影响HNSCC患者预后的因素。使用GSEA软件预测FTH1可能参与调控的信号通路。结果FTH1在HNSCC中高表达,且与肿瘤分期有关(均P<0.05)。FTH1高表达的HNSCC患者总生存率降低(P<0.05)。单因素Cox分析结果显示,高表达的FTH1和肿瘤分期均是影响HNSCC患者的预后因素(均P<0.05)。多因素Cox分析结果显示,肿瘤分期和性别均是影响HNSCC患者的预后因素(均P<0.05)。FTH1的通路富集分析显示,FTH1的高表达样本显著富集到溶酶体、谷胱甘肽代谢、磷酸戊糖途径及癌症通路等基因集。结论FTH1可作为HNSCC的临床预后标志物。
基金supported by the grants National Natural Science Foundation of China (Nos. 81874380 and 82022075, to Xinbing Sui81730108 and 81973635, to Tian Xie)+4 种基金Zhejiang Provincial Natural Science Foundation of China for Distinguished Young Scholars (No. LR18H160001, to Xinbing Sui)Zhejiang Provincial Natural Science Foundation of China (Nos. LQ20H160013, Ting DuanLQ21H160038, to Jiao Feng)Zhejiang Province Science and Technology Project of TCM (Nos. 2019ZZ016, to Xinbing Sui2020ZQ046, to Ruonan Zhang, China)。
文摘Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation.Currently,the therapeutic role of ferroptosis on cancer is gaining increasing interest.Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types;however,the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown.In the study,we investigated the effect of baicalin on bladder cancer cells5637 and KU-19-19.As a result,we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells.Subsequently,we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo,accompanied by reactive oxygen species(ROS) accumulation and intracellular chelate iron enrichment.The ferroptosis inhibitor deferoxamine but not necrostatin-1,chloroquine(CQ),N-acetyl-L-cysteine,L-glutathione reduced,or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone(Z-VAD-FMK) rescued baicalin-induced cell death,indicating ferroptosis contributed to baicalin-induced cell death.Mechanistically,we show that ferritin heavy chain1(FTH1) was a key determinant for baicalin-induced ferroptosis.Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells.Taken together,our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis,which will hopefully provide a prospective compound for bladder cancer treatment.
