化疗耐药是宫颈腺癌（ADC）治疗失败的主要原因，迄今为止尚未找到有效的治疗方法。我们先前利用基因芯片在宫颈腺癌细胞（HeLa）和宫颈腺癌顺铂耐药细胞（HeLa/DDP）中鉴定了差异表达的酪氨酸酶（KYNU）mRNA。然而，KYNU在宫颈腺癌顺铂耐药中的作用和潜在机制尚不清楚。我们验证了ADC患者细胞和组织中KYNU的表达，并分析其与患者预后的相关性。构建了一个稳定的KYNU mRNA沉默的HeLa/DDP细胞系。然后，我们使用CCK8试验检测细胞存活率，利用Transwell试验评估细胞迁移和增殖，使用流式细胞术检测细胞凋亡。在ADC转移性原位模型中评估KYNU沉默对顺铂敏感性的影响。进行免疫组化染色以确定相关药物耐药相关蛋白表达的变化，通过研究KYNU介导的耐药机制探索潜在机制。KYNU在HeLa/DDP细胞和组织中过度表达，并与ADC患者预后不良相关。KYNU mRNA沉默后，HeLa/DDP细胞在顺铂环境中的侵袭、迁移和增殖显著减少，而HeLa/DDP细胞的凋亡率显著增加。同时，KYNU沉默改善了ADC在体内的DDP敏感性。此外，KYNU沉默降低了CD34和与药物耐药相关的蛋白P-gp、MRP1和GST-π的表达，增加了促凋亡调控蛋白Bax的水平。缺乏KYNU通过抑制细胞增殖、迁移和侵袭，促进DDP耐药ADC细胞的凋亡，在体外增强了DDP敏感性。此外，KYNU沉默提高了ADC的药物敏感性。结果表明，KYNU参与了宫颈腺癌的化疗耐药。© 2023年。Springer Nature旗下的BioMed Central Ltd.

Chemotherapy resistance is a leading cause of treatment failure in cases of cervical adenocarcinoma (ADC), and no effective treatment approach has yet been found. We previously identified the differentially expressed kynureninase (KYNU) mRNA in cervical adenocarcinoma cells (HeLa) and cervical adenocarcinoma cisplatin resistance cells (HeLa/DDP) using gene chips. However, the role and potential mechanism of KYNU in the cisplatin resistance of cervical adenocarcinoma remain unclear.We verified the expression of KYNU in the cells and tissues of ADC patients and analyzed its correlation with patient prognosis. A stable HeLa/DDP cell line with KYNU mRNA knockdown was constructed. We then used a CCK8 assay to detect cell survival, a transwell assay to evaluate cell migration and proliferation and flow cytometry to measure apoptosis. The effect of KYNU silence on cisplatin sensitivity was evaluated in an orthotopic model of metastatic ADC. Immunohistochemistry was performed to determine the changes in relevant drug resistance-associated protein expression, aiming to explore the underlying mechanism of KYNU-mediated drug resistance.KYNU is overexpressed in HeLa/DDP cells and tissues and is associated with the poor prognoses of patients with ADC. After KYNU mRNA knockdown, the invasion, migration, and proliferation of HeLa/DDP cells in the cisplatin environment significantly reduced, while the apoptosis rate of HeLa/DDP cells significantly increased. Meanwhile, KYNU knockdown improved the DDP sensitivity of ADC in vivo. Furthermore, silencing KYNU decreased the expressions of CD34 and the drug-resistance related proteins P-gp, MRP1, and GST-π and increased the level of the proapoptotic regulatory protein Bax.KYNU deficiency enhanced DDP sensitivity by suppressing cell proliferation, migration, and invasion and promoting apoptosis in DDP-resistant ADC cells in vitro. Furthermore, KYNU knockdown improved the drug sensitivity of ADC in vivo. The results showed that KYNU is involved in the chemotherapy resistance of cervical adenocarcinoma.© 2023. BioMed Central Ltd., part of Springer Nature.