Department of Otolaryngology, Renhe Hospital of China Three Gorges University, Yichang, Hubei, China (mainland).
Med Sci Monit. 2019 Jan 16;25:475-483. doi: 10.12659/MSM.913180.
BACKGROUND Oxaliplatin (L-OHP) is an important chemotherapy regimen for nasopharyngeal carcinoma (NPC), but can fail due to drug resistance. In this study, the role of Txr1 (taxol-resistant gene 1) in oxaliplatin resistance was investigated. MATERIAL AND METHODS Cell viability assay was carried out using the CellTiter-Glo Luminescent Cell Viability Assay Kit. CNE1 and CNE2 cells were cultured continuously with gradually increasing concentrations of L-OHP for 6 months to establish drug-resistant cell lines. Autophagy was detected by electron microscopy. Txr1 expression in NPC cells was detected via Western blotting and real-time quantitative PCR (qRT-PCR). RESULTS In L-OHP-resistant CNE1/L-OHP and CNE2/L-OHP cells, mRNA and protein expression of Txr1 increased compared to the parental cells, and downregulation of Txr1 re-sensitized drug-resistant cells to L-OHP. Moreover, we found that Txr1-mediated L-OHP resistance was associated with increased autophagy. Txr1-overexpression cells developed L-OHP resistance and a high level of autophagy. Inhibiting autophagy using 2 different methods - inhibition of autophagy-related gene expression and autophagy inhibitor - attenuated L-OHP resistance of NPC cells. CONCLUSIONS We conclude that the detection of Txr1 might become a good indicator to evaluate the treatment and prognosis of nasopharyngeal carcinoma. Our data suggest that further investigation of Txr1 in the setting of L-OHP resistance is warranted.
奥沙利铂（L-OHP）是鼻咽癌（NPC）的重要化疗方案，但由于耐药性而失效。在本研究中，研究了 Txr1（紫杉醇耐药基因 1）在奥沙利铂耐药中的作用。
使用 CellTiter-Glo 发光细胞活力测定试剂盒进行细胞活力测定。将 CNE1 和 CNE2 细胞连续培养并用逐渐增加浓度的 L-OHP 处理 6 个月，以建立耐药细胞系。通过电子显微镜检测自噬。通过 Western blot 和实时定量 PCR（qRT-PCR）检测 NPC 细胞中的 Txr1 表达。
在 L-OHP 耐药的 CNE1/L-OHP 和 CNE2/L-OHP 细胞中，Txr1 的 mRNA 和蛋白表达与亲本细胞相比增加，下调 Txr1 可使耐药细胞重新对 L-OHP 敏感。此外，我们发现 Txr1 介导的 L-OHP 耐药与自噬增加有关。Txr1 过表达细胞产生 L-OHP 耐药和高水平自噬。使用 2 种不同方法（抑制自噬相关基因表达和自噬抑制剂）抑制自噬可减弱 NPC 细胞的 L-OHP 耐药性。
我们得出结论，检测 Txr1 可能成为评估鼻咽癌治疗和预后的良好指标。我们的数据表明，需要进一步研究 Txr1 在 L-OHP 耐药中的作用。
