诱导铁死亡：逆转胰腺癌对吉西他滨化疗耐药性的新策略

肖麟; 郑楷炼; 张佳鑫; 张乐水; 金钢

doi:10.12449/JCH250737

诱导铁死亡：逆转胰腺癌对吉西他滨化疗耐药性的新策略

DOI: 10.12449/JCH250737

海军军医大学长海医院肝胆胰脾外科，上海 200433

基金项目:

国家自然科学基金面上项目 (82172712);

海军军医大学校级基础医学研究课题面上孵化项目 (2022MS013)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：肖麟负责拟定写作思路，绘制图片和论文撰写；金钢、郑楷炼负责课题设计；张佳鑫、张乐水负责文献收集整理；郑楷炼负责指导修改论文并最终定稿。

详细信息

通信作者:
郑楷炼， zhengkl828@126.com （ORCID： 0000-0002-7341-0639）

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出版历程
- 收稿日期: 2024-10-07
- 录用日期: 2024-12-04
- 出版日期: 2025-07-25

Inducing ferroptosis：A novel strategy to reverse gemcitabine resistance in pancreatic cancer

Department of Hepatobiliary Pancreatic and Splenic Surgery，Changhai Hospital，Navyl Medical University，Shanghai 200433，China

Research funding:

General Project of National Natural Science Foundation of China (82172712);

General Incubation Program of Basic Medical Research of Naval Medical University (2022MS013)

More Information

Corresponding author: ZHENG Kailian， zhengkl828@126.com （ORCID： 0000-0002-7341-0639）

摘要

摘要:
胰腺癌是一种高度恶性的消化系统肿瘤，患者5年生存率远低于其他恶性肿瘤。吉西他滨（GEM）作为胰腺癌的主要化疗药物，其疗效常受限于肿瘤的化疗耐药性。本文介绍了胰腺癌中存在的细胞内源性和非细胞自主机制两种GEM耐药机制，归纳了通过调节多不饱和脂肪酸过氧化、铁代谢调控和抗氧化系统诱导细胞铁死亡，可以增强胰腺癌细胞对GEM的敏感性，旨在深入分析铁死亡与GEM耐药机制的关系，并为胰腺癌的临床治疗提出新的方向。
- 铁死亡 /
- 胰腺肿瘤 /
- 抗药性，肿瘤 /
- 吉西他滨
Abstract:
Pancreatic cancer is a highly malignant tumor of the digestive system， with a significantly lower five-year survival rate than other malignancies. Gemcitabine （GEM） is the primary chemotherapeutic agent for pancreatic cancer， but its efficacy is often limited by chemotherapy resistance of tumor. This article elaborates on the intrinsic cellular mechanism and non-cell-autonomous mechanism of GEM resistance in pancreatic cancer and summarizes how to enhance the sensitivity of pancreatic cancer cells to GEM by inducing ferroptosis through the regulation of polyunsaturated fatty acid peroxidation， iron metabolism control， and antioxidant systems， in order to investigate the association between ferroptosis and GEM resistance mechanisms and provide new directions for the clinical treatment of pancreatic cancer.
- Ferroptosis /
- Pancreatic Neoplasms /
- Drug Resistance， Neoplasm /
- Gemcitabine

HTML全文

注： SLC38A5，溶质载体家族35成员5；Glutamine，谷氨酰胺；FBW7，F框/WD重复结构域蛋白7；NR4A1，核受体亚家族4A组；FAM60A，序列相似度60家族成员A；PPAR，过氧化物酶体增殖物激活受体；ACSL4，长链脂酰辅酶A连接酶4；ARF6，ADP核糖基化因子6；NF2，神经纤维蛋白2；BUB1，苯并咪唑出芽抑制解除同源物蛋白1；MOB1，Mps-结合者激酶激活因子样1。

图 1 PUFA过氧化调节通路

Figure 1. Regulation pathway of PUFA peroxidation

下载: 全尺寸图片幻灯片

注： FTH1，铁蛋白重链多肽1；TF，转铁蛋白；TFR1，转铁蛋白受体1；Ferritin，铁蛋白；Labile Iron Pool，不稳定铁库；CBR1，碳酮还原酶1；Chrysin，白杨素。

图 2 铁代谢调节通路

Figure 2. Regulation pathways of iron metabolism

下载: 全尺寸图片幻灯片

注： DNMT3B，DNA甲基转移酶3B；SLC7A11，溶质载体家族7成员11；CPT1B，肉碱棕榈酰转移酶1（CPT1）家族亚型；SMAD4，SMAD家族成员4；lncRNA MACC1-AS1，MACC1反义RNA1；STK33，丝氨酸/苏氨酸激酶33；HSPA5，热休克蛋白家族A成员5；GDMCN2，吉西他滨-DVDMS@金属有机框架@共价有机框架-NRP2抗体；ARID3A，AT丰富结构域相互作用蛋白3A。

图 3 抗氧化系统调节通路

Figure 3. Regulation pathways of antioxidant system

下载: 全尺寸图片幻灯片

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