Avaliação do potencial antineoplásico da idarrubicina associada ao mebendazol em linhagem de adenocarcinoma gástrico metástatico

Abstract

Gastric cancer represents the fourth and fifth type of tumor with the highest incidence in Brazil, in men and women respectively. Current therapies directed to this type of cancer have an unsatisfactory success rate. Among the possible strategies is the use of specific inhibitors that assist in the interruption of tumor progression. Therefore, the present study evaluated the cytotoxic potential of idarubicin in combination with mebendazole (MBZ) in a metastatic gastric cancer cell line, AGP01. Idarubicin (IDA) capable of inducing DNA damage through intercalation between base pairs, breaking the DNA strand and interacting with the enzyme topoisomerase II and MBZ, in turn, acts through depolymerization of tubulin and subsequent disruption of microtubule function. In view of this, the study aimed to perform in vitro tests to evaluate the efficacy of these drugs alone and in combination in a cell line established from a sample of a patients with metastatic gastric cancer. The data revealed that both IDA and MBZ showed high cytotoxicity in the AGP01 (242nM and 300nM) cell line, with the highest cytotoxic activity being conferred on the association of the substances with the IC50 of 123,9nM for IDA and 153,5nM for the MBZ. In addition, both isolated and associated substances delayed the cell migration process 12 hours after treatment with IDA isolated at the concentration of 121nM when compared to the negative control (p<0.05), 12 hours after the treatment with isolated IDA at the concentration of 242nM when compared to the negative control (p<0.001), 12 hours after treatment in the 123,9nM concentration (IC50 of the IDA combination) and 153,5nM (IC50 of the combination MBZ) when compared to the negative control (p<0.05). In addition, both IDA and MBZ, isolated and in association induced apoptosis in the AGP01 cell line (p<0.001). In addition, it was found that both substances, both alone and in combination, were able to block the cell cycle, in the S phase for IDA and MBZ + IDA and in the G2/M phase for MBZ. It is worth mentioning that this is the first study that associates IDA with MBZ in cancer. In assessing the effects of substances, it is of the utmost importance to note that by combining the substances we find that the dose needed to produce the same effects as the isolated substances has been halved. The results generated by the present study demonstrate that both MBZ and IDA present a very promising anticancer potential for patients with advanced gastric cancer.