Title: 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.