Sunitinib potentiates the cytotoxic effect of electrochemotherapy in pancreatic carcinoma cells

Abstract

Background. The primary treatment for pancreatic cancer is surgical resection; however, many patients present with unresectable locally advanced disease, as their tumors are not limited to the pancreas. Therefore, new local ablative therapies are being investigated as new treatment approaches. One of them is electrochemotherapy (ECT), which potentiates the entry of chemotherapeutic drugs by the application of an electric field to the tumor. Its feasibility and safety were demonstrated in preclinical and clinical studies; however, there is a lack of preclinical studies assessing the actions of different drugs used in ECT, their mechanisms and interactions with other target drugs that are used in clinical practice.

Materials and methods. Therefore, the aim of the study was to determine the cytotoxicity of two chemotherapeutic drugs usually used in ECT (bleomycin and cisplatin) in the BxPC-3 human pancreatic carcinoma cell line and evaluate the interactions of ECT with the targeted drug sunitinib. First, the cytotoxicity of ECT using both chemotherapeutics was determined. In the next part, the interactions of ECT and sunitinib were evaluated through determination of combined cytotoxicity, sunitinib targets and kinetics of cell death.

Results. The results demonstrate that ECT is effective in pancreatic cancer cell line, especially when bleomycin is used with the onset of cell death in the first hours after the treatment, reaching a plateau at 20 hours after the treatment. Furthermore, we provide the rationale for combining ECT with bleomycin and the targeted drug sunitinib to potentiate cytotoxicity.

Conclusions. This treatment combination has clinical potential, and further studies are warranted.