Abrogation of Autophagy by Chloroquine in Neuroendocrine Tumor Cells Treated with mTOR Inhibitors Induces Apoptosis, While Reduction of Cell Proliferation is Due to a Chloroquine, Autophagy Unrelated, Lysosomal Effect

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Introduction: The therapy options for patients with advanced NETs are limited. The mTOR inhibitors (mTORi), Torin1 and NVP-BEZ235, are known to suppress cell proliferation in NETs. However, cancer cells may use mTORi-induced autophagy to prolong survival, evading the anti-cancer effect. Chloroquine (CQ) and hydroxychloroquine (HCQ) have been shown to inhibit autophagy.

Aim(s): To explore the mechanisms underlying the effect of CQ/HCQ and mTORi on cell proliferation, apoptosis and autophagy in a NET cell model.

Materials and methods: BON-1 cells was treated with Torin1, BEZ235, HCQ, CQ. Cell proliferation was examined by XTT and Ki67 staining. Flow cytometry and Western blot were used to assess drugs effect on cell cycle, apoptosis, PI3K/Akt/mTOR and autophagy. siRNA against ATG5 and ATG7 was used to genetically inhibit autophagy.

Conference: 12th Annual ENETSConcerence (2015)

Presenting Author: Avniel- Polak S

Authors: Avniel-Polak S, Leibowitz G, Glaser B, Gross D, Grozinsky-Glasberg S,

Keywords: NETs, autophagy, mTORi ,