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<jats:title>Abstract</jats:title><jats:p>Epithelial ovarian cancer (EOC) is one of the most malignant gynecological tumors with a high mortality rate owing to tumor relapse after anticancer therapies. It is widely accepted that a rare tumor cell population, known as cancer stem cells (CSC), is responsible for tumor progression and relapse; intriguingly, these cells are able to survive nutrient starvation (such as <jats:italic>in vitro</jats:italic> culture in the absence of glucose) and chemotherapy treatment. Recent data also indicated that chemotherapy resistance is associated with autophagy activation. We thus decided to investigate both <jats:italic>in vitro</jats:italic> and <jats:italic>in vivo</jats:italic> the autophagic activity and the effects of the perturbation of this pathway in CSC isolated from EOC ascitic effusions. Ovarian CSC, identified according to their CD44/CD117 co-expression, presented a higher basal autophagy compared with the non-stem counterpart. Inhibition of this pathway, by <jats:italic>in vitro</jats:italic> chloroquine treatment or CRISPR/Cas9 ATG5 knockout, impaired canonical CSC properties, such as viability, the ability to form spheroidal structures <jats:italic>in vitro</jats:italic>, and <jats:italic>in vivo</jats:italic> tumorigenic potential. In addition, autophagy inhibition showed a synergistic effect with carboplatin administration on both <jats:italic>in vitro</jats:italic> CSC properties and <jats:italic>in vivo</jats:italic> tumorigenic activity. On the whole, these results indicate that the autophagy process has a key role in CSC maintenance; inhibition of this pathway in combination with other chemotherapeutic approaches could represent a novel effective strategy to overcome drug resistance and tumor recurrence.</jats:p>
- 出版日期2017-7
