Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.

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Autophagy Inhibition in Childhood Nephroblastoma and the Therapeutic Significance.

Curr Cancer Drug Targets. 2017 Mar 30;:

Authors: Li LJ, Wang YL, Yuan LQ, Gu WZ, Zhu K, Yang M, Zhou D, Lv Y, Li MJ, Zhao ZY, Wang JH, Chen X

Abstract
Autophagy is a physiological pathway characterized by lysosome-dependent 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 prognosis of the metastatic and relapsed cases remains poor. The role of autophagy in nephroblastoma is largely uninvestigated. In this study, 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. Decrease of Beclin 1 level and number of autophagosomes was found in nephroblastoma, 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, a inhibitor of autophagy degradation, further decreased the tumor mass compared with single use of the chemotherapeutics vindesine, although no statistical significance was achieved. 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.

PMID: 28359249 [PubMed - as supplied by publisher]

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