The role and mechanism of lysyl oxidase in fibroblasts in regulating the sensitivity of ovarian cancer to paclitaxel
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1.Department of Gynecology ;2.Nanjing Maternal and Child Health Institute,Women’s Hospital of Nanjing MedicalUniversity(Nanjing Women and Children’s Healthcare Hospital),Nanjing 210004 ; 3.Nanjing Medical Key Laboratoryof Female Fertility Preservation and Restoration,Nanjing 210004 ,China

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R737.31

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    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 and qRT-PCR were performed to analyze the expression levels of LOX in human fibroblasts and mouse fibroblasts(L929)induced by paclitaxel. Results:High expression of LOX was significantly associated with the presence of tumors,poor treatment outcomes,and venous invasion in ovarian cancer. LOX was highly expressed in cancer associated fibroblasts in ovarian cancer. Silencing LOX led to the downregulation of cell adhesion molecule expression. Paclitaxel induced upregulation of LOX expression in fibroblasts. Knocking down LOX in fibroblasts increased the sensitivity of co-cultured fibroblasts and tumor cells to paclitaxel. Conclusion:High expression of LOX is associated with a poor prognosis in ovarian cancer,knocking down LOX in fibroblast may enhance the sensitivity of ovarian cancer to paclitaxel;the mechanism of LOX may linked to alterations in the expression of cell adhesion molecules in cancer-associated fibroblasts. Paclitaxel may upregulate the expression of LOX in fibroblasts.

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王嘉桐,徐圣杰,李姗,徐娟,贾雪梅.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[J].南京医科大学学报(自然科学版英文版),2024,(11):1499-1509.

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  • Received:May 28,2024
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  • Online: November 15,2024
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