A miRNAs profile evolution of triple negative breast cancer cells in the presence of a possible adjuvant therapy and senescence inducer.

PURPOSE

Breast cancer is a highly heterogeneous disease with an increasing number of cases resistant to chemotherapy. To increase the response to therapy, different adjuvant systems are tested, like the case of deuterium-depleted water (DDW).

METHODS

For this study, we selected as in vitro model the triple-negative breast cancer cell line MDA-MB-231 and we performed a series of microscopy-based functional tests (apoptosis, autophagy assays, senescence detection) and microarray evaluation of the miRNA profile in order to evaluate changes induced by cisplatin and DDW treatment at cellular and molecular level.

RESULTS

Cisplatin treatment led to increased mitochondrial activity and autophagy for cells kept in DDW, compared with those in standard conditions (SC). We also observed that cells treated with DDW medium promoted senescence in a higher level than SC. The exosomal miRNAs released in cell culture revealed an altered pattern in the case of cells maintained in DDW compared to SC.

CONCLUSION

DDW was proved to be non-toxic, and, when administered with cisplatin, to slightly increase the senescence of cancer cells, therefore, can be pondered as adjuvant therapeutic agent. However, future studies are needed to be done in order to further elucidate its mechanism of action.