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FTO对神经母细胞瘤细胞对各种化疗药物的敏感性有不同影响。

FTO diversely influences sensitivity of neuroblastoma cells to various chemotherapeutic drugs.

作者信息

Lin Meizhen, Hua Zhongyan, Li Zhijie

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Liaoning Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Pharmacol. 2024 Sep 4;15:1384141. doi: 10.3389/fphar.2024.1384141. eCollection 2024.

Abstract

Chemotherapy resistance is a significant factor in treatment failure in patients with neuroblastoma (NB), and it directly affects patient prognosis. Therefore, identifying novel therapeutic targets to enhance chemosensitivity is essential to improve the cure rate and prognosis of patients with NB. In this study, we investigated the role of FTO in chemosensitivity of NB cells to various chemotherapeutic drugs. Our results showed that high FTO expression was positively correlated with increased survival probability and favorable prognostic factors in patients with NB. FTO overexpression inhibited cell proliferation, whereas FTO knockdown promoted cell proliferation in NB cells. FTO expression alteration had contrasting effects on NB cells' sensitivity to etoposide but had no significant impact on sensitivity to cisplatin. Downregulation of FTO reduced the sensitivity of NB cells to paclitaxel, whereas upregulation of FTO enhanced its sensitivity. Additionally, the sensitivities between patients with lower and higher FTO expression to various chemotherapeutic drugs or small-molecule inhibitors were different. Thus, FTO affects the sensitivities of NB cells differently depending on the different chemotherapeutic drugs and small-molecule inhibitors. This finding may guide physicians and patients choose the appropriate chemotherapeutic drugs or small-molecule inhibitors for treatment.

摘要

化疗耐药是神经母细胞瘤(NB)患者治疗失败的一个重要因素,它直接影响患者的预后。因此,识别新的治疗靶点以增强化疗敏感性对于提高NB患者的治愈率和预后至关重要。在本研究中,我们调查了FTO在NB细胞对各种化疗药物的化疗敏感性中的作用。我们的结果表明,高FTO表达与NB患者生存概率增加和良好预后因素呈正相关。FTO过表达抑制细胞增殖,而FTO敲低促进NB细胞增殖。FTO表达改变对NB细胞对依托泊苷的敏感性有相反影响,但对顺铂敏感性无显著影响。FTO下调降低NB细胞对紫杉醇的敏感性,而FTO上调增强其敏感性。此外,FTO表达较低和较高的患者对各种化疗药物或小分子抑制剂的敏感性不同。因此,FTO根据不同的化疗药物和小分子抑制剂对NB细胞敏感性的影响不同。这一发现可能指导医生和患者选择合适的化疗药物或小分子抑制剂进行治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7630/11409730/1959a7a690a1/fphar-15-1384141-g001.jpg

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