{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:44:16Z","timestamp":1759963456001,"version":"3.40.5"},"reference-count":50,"publisher":"S. Karger AG","issue":"6","license":[{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2015,12,1]],"date-time":"2015-12-01T00:00:00Z","timestamp":1448928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;\/i&gt;&lt;\/b&gt; Everolimus (RAD001), an mTORC1 inhibitor, demonstrated promising, but limited, anticancer effects in neuroendocrine tumors (NETs). Torin1 (a global mTOR inhibitor) and NVP-BEZ235 (a PI3K\/mTOR inhibitor) seem to be more effective than RAD001. Autophagy, a degradation pathway that may promote tumor growth, is regulated by mTOR; mTOR inhibition results in stimulation of autophagy. Chloroquine (CQ) inhibits autophagy. &lt;b&gt;&lt;i&gt;Aim:&lt;\/i&gt;&lt;\/b&gt; To explore the effect of CQ alone or in combination with RAD001, Torin1 or NVP-BEZ235 on autophagy and on NET cell viability, proliferation and apoptosis. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; The NET cell line BON1 was treated with CQ with or without different mTOR inhibitors. siRNA against ATG5\/7 was used to genetically inhibit autophagy. Cellular viability was examined by XTT, proliferation by Ki-67 staining and cell cycles by flow cytometry. Apoptosis was analyzed by Western blotting for cleaved caspase 3 and staining for annexin V; autophagy was evaluated by Western blotting and immunostaining for LC3. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; RAD001, Torin1, NVP-BEZ235 and CQ all decreased BON1 cell viability. The effect of RAD001 was smaller than that of the other mTOR inhibitors or CQ. Torin1 and NVP-BEZ235 markedly inhibited cell proliferation, without inducing apoptosis. CQ similarly decreased cell proliferation, while robustly increasing apoptosis. Treatment with Torin1 or NVP-BEZ235 together with CQ was additive on viability, without increasing CQ-induced apoptosis. Inhibition of autophagy by ATG5\/7 knockdown increased apoptosis in the presence or absence of mTOR inhibitors, mimicking the CQ effects. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; CQ inhibits NET growth by inducing apoptosis and by inhibiting cell proliferation, probably via inhibition of autophagy. CQ may potentiate the antitumor effect of mTOR inhibitors.<\/jats:p>","DOI":"10.1159\/000442589","type":"journal-article","created":{"date-parts":[[2015,11,30]],"date-time":"2015-11-30T22:01:21Z","timestamp":1448920881000},"page":"724-737","source":"Crossref","is-referenced-by-count":18,"title":["Abrogation of Autophagy by Chloroquine Alone or in Combination with mTOR Inhibitors Induces Apoptosis in Neuroendocrine Tumor 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