子宫内膜癌及非典型增生患者血清载脂蛋白AI水平及其模拟肽L4F对子宫内膜癌细胞增殖的抑制作用  

The serum level of apolipoprotein AI in patients with endometrial cancer or atypical endometrial hyperplasia and inhibition of apo AI mimetic peptide L4F on the proliferation of endometrial cancer cells

作　　者：徐郁慧 陈晓军 XU Yu-hui;CHEN Xiao-jun(Department of Gynecology,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China;Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases,Shanghai 200011,China)

机构地区：[1]复旦大学附属妇产科医院妇科,上海200011 [2]上海市女性生殖内分泌相关疾病重点实验室,上海200011

出　　处：《复旦学报（医学版）》2022年第1期1-9,共9页Fudan University Journal of Medical Sciences

基　　金：国家重点技术研发计划(2019YFC1005203);国家自然科学基金(81671417)。

摘　　要：目的探究血清载脂蛋白AI(apolipoprotein AI,apo AI)及其模拟肽L4F在子宫内膜癌(endometrial cancer,EC)及非典型增生(atypical endometrial hyperplasia,AEH)患者中的水平及其作用。方法共纳入134名研究对象,包括41例正常对照受试者,48例子宫内膜AEH患者和45例EC患者。测定和比较其血清总胆固醇(total cholesterol,TCH)、甘油三酯(triglyceride,TG)、高密度脂蛋白(high-density lipoprotein,HDL)、低密度脂蛋白(lowdensity lipoprotein,LDL)、载脂蛋白AI和载脂蛋白B(apo B)水平。L4F处理EC细胞系(HEC-1A和ECC-1),作用浓度为0、5、20、40μg/mL,作用时间为48 h;L4F处理EC类器官,作用浓度为20μg/mL,作用时间为7天。CCK8检测EC细胞系增殖活力。光学显微镜下观察EC类器官形态大小改变。荧光免疫组织化学对Ki67表达进行定量以评估EC类器官的增殖活力。Western blot评估细胞系及类器官AMPK磷酸化水平以及Nanog表达水平。结果子宫内膜AEH组及EC组的血清TCH、TG、HDL、LDL水平与正常对照组相比差异无统计学意义;子宫内膜AEH组[(0.970±0.201)g/L]及EC组[(0.913±0.163 g/L)]血清的apo AI水平均低于正常对照组[(1.129±0.257 g/L)],差异有统计学意义(P<0.001)。L4F抑制EC细胞系以及EC类器官的增殖活力;L4F促进EC细胞的AMPK磷酸化以及抑制Nanog蛋白水平。结论EC及AEH患者血清apo AI处于低水平,apo AI模拟肽L4F对EC具有显著的抗肿瘤作用。Objective To investigate the level and role of apolipoprotein AI(apo AI)and its mimetic peptide L4F in atypical endometrial hyperplasia(AEH)and endometrial cancer(EC)patients.Methods The serum levels of total cholesterol(TCH),triglyceride(TG),high-density lipoprotein(HDL),lowdensity lipoprotein(LDL),apo AI and apolipoprotein B(apo B)were measured in 134 individuals with 41normal control subjects,48 patients with AEH and 45 patients with EC.EC cell lines(HEC-1A and ECC-1)were treated with L4F at 0,5,20,40μg/mL for 48 hours and EC-derived organoids(EC organoids)were treated with 20μg/mL L4F for 7 days.Cell proliferation assay was performed to assess the viability of EC cell lines.The morphology and size of organoids were assessed by optical microscope.The quantification of Ki67 expression was achieved by fluorescence immunohistochemistry to test the survival of EC-derived organoids.Western blot was performed to assess the activation of AMPK and the expression of Nanog.Results There was no significant correlation between AEH or EC groups compared with normal group for the serum level of TCH,TG,HDL and LDL.The serum level of apo AI was significantly lower in AEH group[(0.970±0.201)g/L]and EC group[(0.913±0.163)g/L]than that in normal group[(1.129±0.257)g/L](P<0.001).We found that L4F inhibited the proliferation of EC cell lines and suppressed the survival of EC organoids.Moreover,L4F activated the phosphorylation of AMPK and downregulated the expression of Nanog.Conclusion Serum apo AI is low in patients with AEH and EC,and apo AI mimetic peptide L4F has remarkable antitumor effect on endometrial cancer.

关 键 词：子宫内膜癌(EC) 非典型增生(AEH) 载脂蛋白AI(apo AI) 肿瘤类器官 

分 类 号：R737.33[医药卫生—肿瘤]