Amide-Linked Local Anesthetics Alter Tumor Biology in a Complex Human Tissue Model of Non-Small Cell Lung Adenocarcinoma.

Abstract

Amide local anesthetics (LA) affect tumor burden in various preclinical studies, possibly via their anti-inflammatory properties. However, a translation into clinical evidence is still lacking. Here, effects of LA at clinically relevant concentrations are assessed using a human ex vivo tumor model of patient-derived tumor slice cultures from nine patients with non-small cell lung cancer. Tumors are cultivated for four days and treated with LA in absence/presence of cisplatin. Tumor cell proliferation and apoptosis as well as expression of intercellular adhesion molecule-1 and macrophage polarization are assessed using immunofluorescent imaging. Tumor specimens are considered to be "Responders", when a change in proliferation and/or apoptosis by >50% compared to untreated slices occurred. Five of nine samples are "Responders", in which the LA exerted effects comparable to cisplatin. Even at clinically relevant concentrations of LA, a strong anti-tumoral effect is observable in patient-derived tumor slice cultures with complex structures of the tumor microenvironment highlighting the LA effect on the tumor itself and its surroundings, without any interference by other leukocytes or neuronal stimulation. The diverse reaction to LA treatment also emphasizes the importance of biomarkers to determine the tumor phenotypes, which may benefit from LA treatment.