Co-targeting the Endocannabinoid System (ES) and mTOR in NEN potentiates their anti-tumour effect via unique metabolic changes

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Introduction: The current treatment of neuroendocrine neoplasms (NEN) has limited efficacy, highlighting the need for novel therapeutic approaches. We have previously shown the potential therapeutic benefit when combining ES blocking with Everolimus (Eve).

Aim(s): To reveal the functional metabolic changes that underline the synergistic anti-tumour effect of co-targeting NEN with Eve and ES blocking.

Materials and methods: NCI-H727 cells were treated with Eve, ES blocking (CB1 receptor antagonists, CB1RA), or both versus sham treatment. Treatment efficacy was tested in vitro by measuring cell viability with WST1 and cell cycle staining, and in vivo by measuring xenograft tumour size during treatment. XF cell Mito stress test kit was used to measure mitochondrial respiration and evaluate cells glycolytic state. The metabolic profile and metabolic flux of NEN cells were determined by using 13C-glucose labelling and LC-MS analysis.

Conference:

Presenting Author: Avniel-Polak S

Authors: Avniel-Polak S, Kogot-Levin A, Abramovich I, Agranovich B, Polak D,

Keywords: Neuroendocrine neoplasm, Endocannabinoid system, Everolimus, metabolic Changes, metabolomics,