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.
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