抑制SCD1活性对调节脂肪酸代谢途径和抑制宫颈癌细胞肿瘤生物学行为的作用  

Effect of SCD1 inhibition on fatty acid metabolism pathway and the biological behavior of cervical cancer cells

作　　者：于军琴 卢丹 范兰玲 杨永国 田华 YU Junqin;LU Dan;FAN Lanling;YANG Yongguo;TIAN Hua(Department of Obstetrics and Gynecology,Jiangdu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225200,China;Department of Obstetrics and Gynecology,Jiangsu Subei People’s Hospital,Yangzhou 225000,China;Department of Pathology,Jiangdu People’s Hospital Affiliated to Yangzhou University,Yangzhou 225200,China)

机构地区：[1]扬州大学附属江都人民医院妇产科,江苏扬州225200 [2]苏北人民医院妇产科,江苏扬州225000 [3]扬州大学附属江都人民医院病理科,江苏扬州225200

出　　处：《中国医科大学学报》2025年第2期115-120,共6页Journal of China Medical University

基　　金：吴阶平医学基金会临床科研专项资助基金(320.6750.2019-01-08)。

摘　　要：目的 探究抑制硬脂酰辅酶A去饱和酶1 (SCD1)活性对宫颈癌细胞肿瘤生物学行为的作用,并检测其中脂肪酸代谢的分子机制。方法 收集48例宫颈癌患者的癌组织标本和48例子宫肌瘤患者的正常宫颈组织标本。采用免疫组织化学SP染色法和实时定量PCR检测宫颈癌组织与正常宫颈组织中SCD1表达的差异;采用MTS法检测细胞存活率;采用EdU染色观察细胞增殖情况;采用体外划痕实验和Transwell小室实验检测细胞的迁移和侵袭能力;采用免疫荧光染色检测上皮-间质转化标志物E-钙黏蛋白(E-cadherin)和波形蛋白(vimentin)的表达;采用实时定量PCR测定脂肪酸代谢基因SREBP1、ACLY、ACC和FAS的表达量;采用尼罗红荧光染色观察细胞内脂滴含量。结果 宫颈癌组织中SCD1阳性表达率和SCD1 mRNA相对表达量高于正常宫颈组织(P <0.05)。不同浓度的MF-438处理HeLa细胞后,细胞存活率和EdU阳性细胞率下降,划痕闭合率、迁移细胞数和侵袭细胞数减少,E-cadherin荧光染色强度增加,vimentin荧光染色强度减弱,SREBP1、ACLY、ACC、FAS mRNA相对表达量均下调,脂滴含量减少,并呈浓度依赖性(均P <0.05)。结论 SCD1在宫颈癌组织中异常高表达,抑制SCD1活性能够明显降低HeLa细胞的脂质代谢水平,并抑制细胞增殖、迁移、侵袭及上皮-间质转化。Objective To investigate the effect of inhibiting stearoyl-CoA desaturase 1(SCD1) activity on the biological behavior of cervical cancer cells and elucidate the molecular mechanisms related to fatty acid metabolism.Methods Cancer tissues were collected from 48 patients with cervical cancer,whereas normal cervical tissues were obtained from 48 patients with uterine fibroids.Immunohistochemical SP staining and real-time quantitative PCR were performed to assess differences in SCD1 expression.The MTS assay was used to determine cell viability,and EdU staining was conducted to evaluate cell proliferation.Cell migration and invasion abilities were analyzed using in vitro scratch assay and Transwell chamber assay.Immunofluorescence staining was performed to detect E-cadherin and vimentin expression.Real-time quantitative PCR was used to measure the mRNA expression levels of SREBP1,ACLY,ACC,and FAS.Nile red fluorescence staining was applied to observe intracellular lipid droplet content.Results The positive expression rate of SCD1 and the relative expression level of SCD1 mRNA were significantly higher in cervical cancer tissues than in normal cervical tissues(P < 0.05).Treatment of He La cells with varying concentrations of MF-438 led to significant reductions in cell viability,EdU-positive cell rate,scratch closure rate,and the number of migrating and invading cells.Additionally,the fluorescence intensity of E-cadherin increased,whereas that of vimentin decreased.The relative expression levels of SREBP1,ACLY,ACC,and FAS mRNA were downregulated,and intracellular lipid droplet content decreased in a concentration-dependent manner(P < 0.05).Conclusion Inhibition of SCD1 activity significantly reduced lipid metabolism in HeLa cells and suppressed malignant biological behaviors,including proliferation,migration,invasion,and epithelial-mesenchymal transition.

关 键 词：宫颈癌 HELA细胞 硬脂酰辅酶A去饱和酶1 脂肪酸代谢 生物学行为 

分 类 号：R737.33[医药卫生—肿瘤]