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Open Access 01-12-2017 | Primary Research

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

Authors: María Fernanda Rubio, María Cecilia Lira, Francisco Damián Rosa, Adrían Dario Sambresqui, María Cecilia Salazar Güemes, Mónica Alejandra Costas

Published in: Cancer Cell International | Issue 1/2017

Abstract

Background

RAC3 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.

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 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.

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 design new improved therapeutic strategies in the future.

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Title: RAC3 influences the chemoresistance of colon cancer cells through autophagy and apoptosis inhibition
Authors: María Fernanda Rubio
María Cecilia Lira
Francisco Damián Rosa
Adrían Dario Sambresqui
María Cecilia Salazar Güemes
Mónica Alejandra Costas
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Cancer Cell International / Issue 1/2017
Electronic ISSN: 1475-2867
DOI: https://doi.org/10.1186/s12935-017-0483-x

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Abstract

Background

Methods

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