Page 33 - 南京医科大学自然版

第44卷第11期 南京医科大学学报（自然科学版）
2024年11月 Journal of Nanjing Medical University（Natural Sciences） ·1499 ·

·基础研究·

成纤维细胞中赖氨酰氧化酶调控卵巢癌紫杉醇敏感性的作用

及机制探讨

王嘉桐 ，徐圣杰 ，李 姗 ，徐 娟 ，贾雪梅 1，3*
1
1
2
1，3
南京医科大学附属妇产医院（南京市妇幼保健院）妇科，医学研究中心，江苏 南京 210004；南京市女性生育力保护及重塑
1 2 3
医学重点实验室，江苏 南京 210004

［摘 要］ 目的：探讨赖氨酰氧化酶（lysyl oxidase，LOX）在卵巢癌中的表达模式、可能的作用机制，以及其表达与卵巢癌临床
特征及治疗结局的相关性。方法：利用人类癌症基因组图谱（the Cancer Genome Atlas，TCGA）分析 LOX表达与卵巢癌临床病
理特征、治疗结局及预后的相关性；利用TISCH2数据库研究LOX在卵巢癌微环境不同细胞中的表达特征；免疫组化分析LOX
在卵巢癌组织中的表达情况；利用siRNA转染技术沉默LOX基因，并通过转录组测序分析LOX沉默组及对照组细胞差异表达
基因；通过基因集富集分析（gene set enrichment analysis，GSEA）LOX 沉默组及对照组差异表达的信号通路蛋白并通过 qRT⁃
PCR验证；通过测定半数致死剂量（half⁃maximal inhibitory concentration，IC50）分析成纤维细胞中敲降LOX对卵巢癌紫杉醇敏感
性的影响；通过 Western blot 及qRT⁃PCR 分析紫杉醇作用下人纤维细胞和鼠纤维细胞中（L929）中LOX表达变化。结果：LOX
高表达与卵巢癌的肿瘤存在、治疗结局差及静脉侵犯显著相关；在卵巢癌中，LOX在成纤维细胞中表达较高；沉默LOX可下调
细胞黏附分子的表达；紫杉醇可诱导成纤维细胞中LOX表达上调；成纤维细胞中敲降LOX可增加共培养的成纤维细胞与肿瘤
细胞对紫杉醇的敏感性。结论：LOX高表达与卵巢癌的不良预后相关，敲降LOX可提高卵巢癌对紫杉醇的化疗敏感性；其作
用机制可能与改变成纤维细胞中细胞黏附分子表达相关；紫杉醇可上调成纤维细胞中LOX的表达。
［关键词］ 赖氨酰氧化酶；卵巢癌；细胞黏附分子；紫杉醇
［中图分类号］ R737.31 ［文献标志码］ A ［文章编号］ 1007⁃4368（2024）11⁃1499⁃11
doi：10.7655/NYDXBNSN240547

The role and mechanism of lysyl oxidase in fibroblasts in regulating the sensitivity of
ovarian cancer to paclitaxel

1 1 2 1，3 1，3*
WANG Jiatong ，XU Shengjie ，LI Shan ，XU Juan ，JIA Xuemei
Department of Gynecology，Nanjing Maternal and Child Health Institute，Women’s Hospital of Nanjing Medical
1 2
University（Nanjing Women and Children’s Healthcare Hospital），Nanjing 210004；Nanjing Medical Key Laboratory
3
of Female Fertility Preservation and Restoration，Nanjing 210004，China

［Abstract］ Objective：To investigate the expression patterns and underlying mechanisms of lysyl oxidase（LOX）in ovarian cancer，
and to explore the correlation between its expression level and the clinical characteristics and therapeutic outcomes of the disease.
Methods：The correlations of high LOX expression with the clinicopathological features，treatment outcomes，and prognosis of ovarian
cancer were analyzed by the Cancer Genome Atlas（TCGA）. The expression characteristics of LOX mRNA in different ovarian cancer
cells in the tumor microenvironment were explored by the TISCH2 database. The expression pattern of LOX in ovarian cancer tissues
were confirmed through immunohistochemistry. We used siRNA transfection technology to silence the expression and LOX，and then
aralyzed the differentially expressed genes between LOX⁃silencing and control fibroblasts through RNA sequencing，followed by Gene
Set Enrichment Analysis（GSEA）to identify the signaling pathways that were differentially enriched between the LOX⁃silenced and the
control groups，with subsequent validation through qRT ⁃ PCR. The effect of knocking down LOX in fibroblast on the sensitivity of
ovarian cancer to paclitaxel was analyzed by determining the half⁃maximal inhibitory concentration（IC50）. Furthermore，Western blot

［基金项目］ 国家自然科学基金（81872126）
∗
通信作者（Corresponding author），E⁃mail：xmjia@njmu.edu.cn