Synergic Effects of Anticancer Peptide CIGB-552 and Cisplatin in Lung Cancer Models

Abstract Non-small cell lung cancer constitutes one the most frequent and lethal forms of the disease. The antitumor peptide CIGB-552 is a new targeted anticancer therapy which molecular mechanism is associated with the inhibition of the transcription factor NF-kB, mediated by COMMD1 protein stabilization. However, its pharmacological potential in combination with chemotherapy is unknown. In this study, we examined the antiproliferative capacity of CIGB-552 in combination with chemotherapeutic agents in the non-small cell lung cancer cell line NCI-H460 and we confirmed drug interactions in vivo, in a mouse model of TC-1 lung cancer. We focus our research in the combination of CIGB-552 and the antineoplastic agent Cisplatin (CDDP) in a concomitant treatment. Our results demonstrate a clear synergic effect between 37.5 µM of CIGB-552 and 5 µM of CDDP under concomitant scheme, on proliferation inhibition, cell cycle arrest, apoptosis induction and oxidative stress response. The effect of CIGB-552 (1 mg/kg) and CDDP (0.4 mg/kg) administrated as a combined therapy was demonstrated in vivo in the TC-1 murine model where the combination achieved an effective antitumor response, without any deterioration signs or side effects. These findings demonstrate the efficacy of the concomitant combination of both drugs in preclinical studies and support the use of this therapy in clinical trials.