《生命科学》 2022, 34(5): 506-516
微量元素与肺癌研究进展
摘 要：
近年来，微量元素对肺癌发生、发展及预后的影响被逐步发现。肺癌细胞铁摄取增加、外排减少，胞内积累的铁可通过触发p53 降解、激活CDK1/GP130/STAT3 通路、提高肺癌细胞干性、参与铁硫簇的合成等途径促进肺癌的发展；同时，铁还可参与肺癌细胞铁死亡过程以及提高肺癌免疫微环境中M1 型巨噬细胞的比例而抑制肺癌的发展。锌可介导肺癌细胞发生凋亡、铁死亡以及失巢性凋亡，还可通过抑制肺癌细胞干性、减缓端粒缩短等方式抑制肺癌的发展。铜与ULK1 激酶结合有利于肺癌细胞在应激条件下的存活。硒可激发肺癌免疫微环境抑制肺癌发展，但硒蛋白GPX4 可保护肺癌细胞免受氧化应激损伤而促进肺癌发展。相比于健康人群，肺癌患者血清中钴、铬、镍等元素含量上调，锰元素含量下调，提示这些元素也可能参与肺癌的发展。从元素间串话角度分析，铜/ 锌比数值越高，肺癌患者预后越差。本文就微量元素与肺癌的研究进展作一综述，以期为肺癌发病机制的阐明和防治提供新的线索。
通讯作者：朱 波 , Email:zhubo@cpu.edu.cn 华子春 , Email:zchua@nju.edu.cn
Abstract:
Lung cancer is one of the most malignant tumors with extremely high morbidity and mortality. Current treatment options for lung cancer include surgery, radiotherapy, and chemotherapy. However, the prognosis of patients with lung cancer remains poor. In recent years, the importance of trace elements in cancer tumorigenesis, malignant progression, and prognosis has been highlighted. Increased uptake and decreased efflux of iron was observed in lung cancer cells. Intracellular iron accumulation promoted lung cancer development via several pathways, including promoting p53 degradation, activating the CDK1/GP130/STAT3 pathway, maintaining tumor stemness, and affecting iron-sulfur clusters synthesis. On the contrary, iron could also inhibit lung cancer development via participating in ferroptosis and increasing the proportion of M1 macrophages in lung cancer immune microenvironment. Zinc played an anti-tumor role via triggering apoptosis, ferroptosis, and anoikis, downregulating tumor stemness and telomere shortening in lung cancer cells. The interaction of copper with ULK1 promoted survival of lung cancer cells under stress. Selenium played an anti-tumor role via regulating tumor immune microenvironment in lung cancer. However, the selenoprotein GPX4 promoted lung cancer progression via its anti-oxidative functions. Increased cobalt, chromium, and nickel levels and decreased manganese level were observed in the serum of patients with lung cancer, indicating the involvement of these elements in lung cancer progression. Higher copper/zinc ratio predicted poorer prognosis for lung cancer, highlighting the importance of crosstalk among trace elements. This review summarizes the recent progress in elucidating the potential effects of trace elements on the prevention and treatment of lung cancer and underlying mechanisms.
Communication Author：ZHU Bo , Email:zhubo@cpu.edu.cn HUA Zi-Chun , Email:zchua@nju.edu.cn
