摘要
目的 总结胆固醇代谢在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)发生发展中的重塑及靶向胆固醇代谢在治疗PDAC的研究进展.方法 检索近年来有关胆固醇代谢在PDAC发生发展及诊疗的相关文献并进行综述.结果 PDAC肿瘤细胞代谢物影响癌基因或抑癌基因的表达,肿瘤细胞内相关信号调控影响胆固醇代谢,表现为胆固醇从头合成和酯化增多、外流减少等;肿瘤细胞还通过胆固醇代谢调控肿瘤免疫微环境或肿瘤基质的形成.抑制胆固醇代谢可抑制PDAC肿瘤细胞的增殖、侵袭、迁移等恶性生物学行为,且联合靶向胆固醇代谢的治疗具有协同抗PDAC的作用.结论 不论是PDAC肿瘤细胞内还是肿瘤微环境内均发生胆固醇代谢重塑,且与PDAC发生发展、侵袭转移及治疗效果密切相关;靶向胆固醇代谢或联合应用化疗药物能够起到抗癌效果.但需要更多的研究来支持实现胆固醇代谢调控在临床治疗的转化应用.
Abstract
Objective To summarize the remodeling of cholesterol metabolism in the occurrence and progression of pancreatic ductal adenocarcinoma(PDAC),and to review the research progress on targeted cholesterol metabolism in the treatment of PDAC.Method Relevant literatures on cholesterol metabolism in the occurrence,development,and diagnosis and treatment of PDAC in recent years were searched and reviewed.Results Metabolites of PDAC tumor cells affected the expression of oncogenes or tumor suppressor genes.Signaling regulation within tumor cells affects cholesterol metabolism,characterized by increased de novo cholesterol synthesis and esterification,and reduced efflux.Tumor cells also regulated tumor immune microenvironment or tumor stroma formation through cholesterol metabolism.Inhibiting cholesterol metabolism could suppress the proliferation,invasion and migration of PDAC tumor cells,and combination therapy targeting cholesterol metabolism had a synergistic anti-PDAC effect.Conclusions Remodeling of cholesterol metabolism occurs in both PDAC tumor cells and the tumor microenvironment,and is closely related to the occurrence,development,invasion,metastasis,and treatment response of PDAC.Targeting cholesterol metabolism or combined application with chemotherapy drugs can have anticancer effects.However,more research is needed to support the translation of cholesterol metabolism regulation into clinical treatment applications.
基金项目
四川省自然科学基金项目(2023NSFSC0726)
NETL
NSTL
万方数据