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

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...

Full description

Saved in:
Bibliographic Details
Published in:Cancer cell international 2017-11, Vol.17 (1), p.111-111, Article 111
Main Authors: Rubio, María Fernanda, Lira, María Cecilia, Rosa, Francisco Damián, Sambresqui, Adrían Dario, Salazar Güemes, María Cecilia, Costas, Mónica Alejandra
Format: Article
Language:English
Subjects:
5-Fluorouracil
Antigens
Apoptosis
Autophagy
Breast cancer
Cancer therapies
Caspase-3
Chemoresistance
Chemotherapy
Colon cancer
Colorectal cancer
Colorectal carcinoma
Hypoxia
Inhibition
Kinases
Medical prognosis
Medical screening
Metastasis
Oxaliplatin
Phagocytosis
Primary Research
RAC3
Ribonucleic acid
RNA
Sensitivity
Tumorigenesis
Viability
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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. 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. 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.
ISSN:1475-2867
1475-2867
DOI:10.1186/s12935-017-0483-x