Cannabinoids and the Endocannabinoid System as modulatory targets in neuroendocrine neoplasms (NENs) – Possible mechanisms and antitumor efficacy

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Introduction: Patients with unresectable NENs are offered a variety of non-curable therapeutic options, which eventually fail due to drug resistance (DR). Increasing evidence suggest an anticancer trait of cannabinoids, via cellular pathways including mTOR, known to be associated with DR development. Still, limited data exist on the anti-cancer effects of cannabinoids in NENs.

Aim(s): To understand the possible anti-tumor role of the cannabinoids and the endocannabinoid system in NENs, and their ability to overcome resistance to everolimus (Eve).

Materials and methods: The endocannabinoid receptors (ER) expression on NENs cell lines of lung (NCI-H727) and pancreatic (BON1) origin and on human samples was examined using FACS/immunofluorescence staining and RNA-Seq. Cells were treated with multiple cannabinoids extracts (CE). Viability and apoptosis were examined using WST-1 and Annexin/PI. ER blocking with specific antagonists examined CE-induced toxicity. The effect of Eve ± CE/ER-antagonists on cell viability was examined.

Conference:

Presenting Author: Avniel-Polak S

Authors: Avniel-Polak S, Polak D, Oleinikov K, Gross D, Wald O,

Keywords: neuroendocrine neoplasm, cannabinoids, endocannabinoid system, cannabis extracts, everolimus,