摘要
背景:自噬是一种以溶酶体依赖的自身消化为特征的生理途径,以回收受损或多余的细胞含量。解除自噬的管制会妨碍维修工作细胞内动态平衡并促进肿瘤发生。然而,在抗肿瘤治疗中,自噬激活促进了耐药性的发展。因此,自噬已被确认为i。肿瘤的重要途径和治疗靶点。肾母细胞瘤(Wilm‘s瘤)是儿童常见的恶性肿瘤。自噬在肾母细胞瘤中的作用尚未被研究。 目的:探讨间变性肾母细胞瘤自噬水平的变化及自噬是否成为治疗的靶点。 方法:在儿童肾母细胞瘤的临床标本中,通过自噬标记物的表达和自噬小体超微结构的存在来评价其自噬活性。使用对自噬抑制剂单独及联合常规化疗药物在体内外的应用进行了研究。 结果:肾母细胞瘤中Beclin 1水平和自噬小体数量减少,提示自噬抑制。此外,在两株间变性肾母细胞瘤细胞中,G 401 aNDSK-NEP 1,自噬抑制剂进一步增强了包括长春新碱和顺铂在内的常规化疗药物的疗效。在G 401裸鼠肿瘤模型中,联合应用氯喹是一种自噬降解抑制剂,与单纯使用化疗药物长春地辛相比,其肿瘤体积进一步减少,但没有统计学意义。 结论:肾母细胞瘤存在自噬解除管制,靶向自噬可作为治疗恶性程度较高的辅助治疗策略。
关键词: 肾母细胞瘤,Wilm‘s肿瘤,自噬,Beclin 1,化疗,联合治疗。
图形摘要
Current Cancer Drug Targets
Title:Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance
Volume: 18 Issue: 3
关键词: 肾母细胞瘤,Wilm‘s肿瘤,自噬,Beclin 1,化疗,联合治疗。
摘要: Background: Autophagy is a physiological pathway characterized by lysosomedependent self-digestion to recycle damaged or superfluous cellular content. Deregulation of autophagy hampers the maintenance of cellular homeostasis and contributes to tumorigenesis. However, during anticancer therapy, autophagy activation contributes to development of resistance. Thus autophagy has been recognized as an important pathway and a therapeutic target in cancer. Nephroblastoma (Wilm's tumor) is a common childhood malignancy. The role of autophagy in nephroblastoma is largely uninvestigated.
Objective: This study is to investigate the change of autophagy level in nephroblastoma, and whether autophagy could be a therapeutic target in anaplastic nephroblastoma.
Method: In clinical samples of childhood nephroblastoma, autophagy activity was evaluated by the expressions of selected autophagy markers as well as the presence of autophagosome ultrastructure. Use of autophagy inhibitors alone and in combination with conventional chemotherapeutics, was studied both in vivo and in vitro.
Results: In nephroblastoma, there was decrease in the Beclin 1 level and the number of autophagosomes, suggesting autophagy inhibition. Furthermore, in two anaplastic nephroblastoma cell lines, G401 and SK-NEP1, autophagy inhibitors further enhanced the efficacy of conventional chemotherapeutics including vincristine and cisplatin. In G401 tumor model established in nude mice, combinational use of chloroquine, an inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved.
Conclusion: Our results suggest that autophagy deregulation is involved in nephroblastoma, and targeting autophagy can serve as a potential adjuvant strategy for the highly malignant cases.
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Cite this article as:
Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance, Current Cancer Drug Targets 2018; 18 (3) . https://dx.doi.org/10.2174/1568009617666170330105433
DOI https://dx.doi.org/10.2174/1568009617666170330105433 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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