Endocrine Abstracts

Finding new preclinical models to study the effects of anticancer drugs is one of the aims of biomedical research. Indeed, testing different in vitro systems can lead to a better understanding of the molecular pathways regulating tumor development and growth, and help to find new therapeutic approaches. This is crucial especially in the settings of pancreatic neuroendocrine tumours (pNET), where one of the main drugs approved for medical treatment is Sunitinib, a multi-targeted receptor kinase inhibitor. Clarifying the effects of this drug may be important to develop more effective medical treatment, therefore we tested Sunitinib on the human pNET cell line, BON1, grown in two different in vitro systems, monolayer and spheroid, in order to understand the different effects of the drug in 2D and 3D settings.

BON1 cells were grown in monolayer and treated with Sunitinib at increasing concentrations (0.25–5 μM). Cell Proliferation Assay and Luminescent Cell Viability Assay were employed to test Sunitinib antiproliferative effects. We found that Sunitinib 5 μM significantly reduced BON1 cell viability by 30% (P<0.01 vs control) after 3 days. Similarly, Sunitinib 5 μM significantly reduced BON1 cell proliferation by 50% (P<0.05 vs control) after 3 days and by 90% (P<0.05 vs control) after 7 days.

Then, BON1 cells were grown in spheroids with Sunitinib at increasing concentrations (0.25–5 μM). Spheroids size was analyzed with ImageJ software after 3 and 7 days. We found that Sunitinib does not affect spheroid size, but induces spheroid disgregation after 7 days of treatment at 5 μM.

These results indicate that measuring spheroid diameter in a 3D system is not the optimal system to assess the antiproliferative effects of Sunitinib on BON1 cells. On the other hand, the differences observed between the employed models could reflect the variations in drug response depending on cell aggregation state.