卵巢癌具有较高的发病率及病死率,严重威胁全世界女性的健康。铁是人体必须微量元素,参与许多细胞生理过程,研究证实肿瘤细胞对铁表现为强烈的依赖,过表达铁代谢相关的蛋白质,这使得铁在肿瘤细胞内蓄积,导致其快速增殖。近年来,铁代谢在卵巢癌中发生发展的作用机制是研究的热点问题。本篇综述讨论了铁代谢异常与卵巢癌的关系,了解铁与铁代谢相关产物在卵巢癌细胞中的变化,为指导卵巢癌的诊治提供一种新的诊疗思路。Ovarian cancer has a high incidence rate and mortality, which seriously threatens the health of women all over the world. Iron is an essential trace element for the human body and participates in many cellular physiological processes. Studies have shown that tumor cells exhibit a strong dependence on iron and overexpress proteins related to iron metabolism, leading to the accumulation of iron in tumor cells and rapid proliferation. In recent years, the mechanism of iron metabolism in the occurrence and development of ovarian cancer has been a hot research topic. This review discusses the relationship between abnormal iron metabolism and ovarian cancer, understanding the changes in iron and iron metabolism related products in ovarian cancer cells, and providing a new diagnostic and therapeutic approach for guiding the diagnosis and treatment of ovarian cancer.
目的:探讨顺铂(cisplatin,DDP)最大可耐受剂量化疗(maximum tolerated dose chemotherapy with DDP,MTD-DDP)和DDP低剂量节拍化疗(low-dose metronomic chemotherapy with DDP,LDM-DDP)对人卵巢癌裸鼠移植瘤的作用及其对移植瘤中乙醛脱氢酶1(aldehyde dehydrogenase 1,ALDH1)表达的影响。方法:建立人卵巢癌SKOV3细胞裸鼠皮下移植瘤模型,并进行MTDDDP和LDM-DDP化疗,观察不同化疗模式对移植瘤生长的影响。制备裸鼠移植瘤原代细胞,并应用流式细胞分选术分选ALDH1阳性细胞。应用平板克隆形成实验和裸鼠体内成瘤实验检测ALDH1阳性细胞的克隆形成能力和裸鼠体内成瘤能力,蛋白质印迹法检测ALDH1阳性细胞中Ki-67、乳腺癌耐药蛋白(breast cancer resistant protein,BCRP)和CD133的表达水平。结果:MTD-DDP和LDM-DDP均可抑制裸鼠移植瘤的生长,LDMDDP的抑瘤作用更明显(P<0.001)。MTD-DDP组移植瘤原代细胞中ALDH1阳性细胞所占比率明显高于对照组(以0.9%氯化钠溶液代替DDP),LDM-DDP组移植瘤原代细胞中ALDH1阳性细胞所占比率明显低于对照组,差异均有统计学意义(P值均<0.001)。ALDH1阳性细胞的平板克隆形成能力(P<0.001)和裸鼠体内成瘤能力均高于ALDH1阴性细胞。ALDH1阳性细胞中Ki-67的表达水平低于ALDH1阴性细胞,而BCRP和CD133的表达水平高于ALDH1阴性细胞,差异均有统计学意义(P值均<0.001)。结论:LDM-DDP抑制卵巢癌裸鼠皮下移植瘤生长的作用较强,并可降低ALDH1阳性细胞所占比率。
