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

Article

Authorship

RUBIO, MARIA FERNANDA ; Lira, María Cecilia ; Rosa, Francisco Damián ; Sambresqui, Adrián Dario ; Salazar Güemes, María Cecilia ; COSTAS, MONICA ALEJANDRA

Date

2017

Publishing House and Editing Place

BioMed Central

Magazine

CANCER CELL INTERNATIONAL, vol. 17 (pp. 1-17) BioMed Central

Summary Information provided by the agent in SIGEVA

Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis 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.Methods: The 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 vi... Background: RAC3 coactivator overexpression has been implicated in tumorigenesis, contributing to inhibition ofapoptosis 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.Methods: The 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.Results: In HCT 116 cells, we found that although 5-fluorouracil was a poor inducer of apoptosis, autophagy wasstrongly induced, while oxaliplatin has shown a similar ability to induce both of them. However, in HCT 116 cellsexpressing a short hairpin RNA for RAC3, we found an increased sensitivity to both drugs if it is compared with controlcells. 5-Fluorouracil and oxaliplatin treatment lead to an enhanced caspase 3-dependent apoptosis and produce anincrease of autophagy. In addition, both process have shown to be trigged faster than in control cells, starting earlierafter stimulation.Conclusions: Our 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 designnew improved therapeutic strategies in the future.