索拉非尼基于Hippo/YAP及PI3K/Akt/mTOR信号通路介导细胞自噬在肝细胞癌中产生耐药机制研究进展
Research progress on mechanism of drug resistance induced by autophagy mediated by Hippo/YAP and PI3K/Akt/mTOR signaling pathways in hepatocellular carcinoma
曹智 1周塏 1陈骋 2梁贤文 2刘路政 3武金才4
作者信息
- 1. 海南医学院临床学院,海南 海口 571199
- 2. 海南省人民医院肝胆胰外科,海南 海口 570311
- 3. 海南医学院第二附属医院介入血管外科,海南 海口 570216
- 4. 海南医学院临床学院,海南 海口 571199;海南省人民医院肝胆胰外科,海南 海口 570311
- 折叠
摘要
肝细胞癌(HCC)是世界上最常见的恶性肿瘤之一,它的形成是一个复杂的过程,其具体形成机制尚不明确,由于大多数HCC患者被诊断出来时已是晚期,通常已丧失良好的手术时机.而靶向药物的出现给当前 HCC患者带来了新的希望,同时还可作为术后治疗措施,在HCC中发挥着巨大的作用.索拉非尼是第一个被用于治疗HCC的靶向药物,它可抑制肝肿瘤组织血管生成和细胞增殖,可诱导肝肿瘤细胞凋亡,进而提高部分肝癌患者的生存率.但据目前研究显示,有50%～60%HCC经治患者对该药物出现了敏感性下降.主要是由于索拉非尼使用后会抑制体内相关信号通路,从而致使耐药的发生,故进一步探索索拉非尼耐药机制,使其逆转索拉非尼耐药对于改善肝癌治疗的预后具有极其重要的临床价值.近些年来,许多学者致力研究索拉非尼通过Hippo/YAP及PI3K/Akt/mTOR信号通路介导细胞自噬与耐药性的产生有着密切联系.并探讨其耐药分子机制,使该领域获得了巨大的发展.因此,本篇文章主要从Hippo/YAP及PI3K/Akt/mTOR信号通路展开,探讨其与细胞自噬之间的关系以及介导的耐药机制,为索拉非尼治疗肝癌产生耐药性提供可靠的科学理论依据.
Abstract
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors in the world.Its formation is a complex process,and the specific mechanism of its formation hasn't been cleared yet.Due to the fact that most HCC patients are diagnosed in the late stage,and they often lose good surgical opportunities.The emergence of targeted drugs has brought new hope to current HCC patients and can also serve as one of the measures for postoperative treatment,playing a huge role in treating HCC.Sorafenib is the first targeted drug used to treat HCC.It can induce apoptosis of liver tumor cells and inhibit proliferation and angiogenesis of liver tumor cells,so it can improve the survival rate of some patients.However,according to current research,50%-60%of HCC patients experience a decrease in sensitivity to the drug.It is mainly because Sorafenib will inhibit relevant sig-naling pathways in vivo after using,which leads to the occurrence of drug resistance,so further exploring the mechanism of Sorafenib resistance and reversing Sorafenib resistance have extremely important clinical value for improving the prognosis of liver cancer treatment.In recent years,many scholars have devoted themselves to studying the close relationship between Sorafenib me-diated autophagy and drug resistance through Hippo/YAP and PI3K/Akt/mTOR signaling pathways.And exploring the molecu-lar mechanisms of drug resistance has led to significant development in this field.Therefore,this article mainly discusses the rela-tionship between Hippo/YAP and PI3K/Akt/mTOR signaling pathways and autophagy,as well as the mechanism of drug resis-tance mediated by them,so as to provide a reliable Scientific theory basis for drug resistance of Sorafenib in the treatment of liver cancer.
关键词
索拉非尼/Hippo/YAP信号通路/PI3K/Akt/mTOR信号通路/细胞自噬/肝细胞癌/耐药机制Key words
Sorafenib/Hippo/YAP signaling pathway/PI3K/Akt/mTOR signaling pathway/Autophagy/Hepatocellu-lar carcinoma/Mechansim of drug resistance引用本文复制引用
基金项目
海南省自然科学基金(821QN391)
海南省自然科学基金(ZDYF2022SHFZ283)
出版年
2024
国家科技期刊平台
NSTL
万方数据