RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition.

MARÍA CECILIA SALAZAR GÜEMES; MARÍA CECILIA LIRA; MARÍA CECILIA SALAZAR GÜEMES; MARÍA CECILIA LIRA; MÓNICA ALEJANDRA COSTAS; FRANCISCO DAMIÁN ROSA; MÓNICA ALEJANDRA COSTAS; FRANCISCO DAMIÁN ROSA; ADRÍAN DARIO SAMBRESQUI; MARÍA FERNANDA RUBIO; ADRÍAN DARIO SAMBRESQUI; MARÍA FERNANDA RUBIO

CANCER CELL INTERNATIONAL

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2017 vol. 17 p. 1 - 17

1475-2867

BackgroundRAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition of apoptosis and autophagy. Both mechanisms are involved in resistance to treatment with chemotherapeutic agents. The aim of this study was to investigate its role in chemoresistance of colorectal cancer.MethodsThe sensitivity to 5-fluorouracil and oxaliplatin in colon cancer cells HT-29, HCT 116 and Lovo cell lines, expressing high or low natural levels of RAC3, was investigated using viability assays.ResultsIn HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy was strongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cells expressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with control cells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce an increase of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlier after stimulation.ConclusionsOur results suggest that RAC3 expression levels influence the sensitivity to chemotherapeutic drugs. Therefore, the knowledge of RAC3 expression levels in tumoral samples could be an important contribution to design new improved therapeutic strategies in the future.