Involvement of RhoGDI2 in the resistance of colon cancer cells to 5-fluorouracil.

Background/aims: The acquisition of resistance to 5-FU is one of the most prominent obstacles to successful chemotherapy, and the mechanisms underlying the resistance are not fully understood. The aim of this study is to identify novel mediators of 5-FU resistance in colon cancer cells.
Methodology: LoVo colon cancer cells were induced to 5-FU resistance in vitro. The global protein profiles between LoVo and its 5-FU resistant derivative cell line LoVo/5-FU were analyzed by two dimensional gel electrophoresis-based comparative proteomics. The identified proteins expression was confirmed by Western blot analysis. The cytotoxicity of 5-FU was measured in LoVo/5-FU after knockdown of RhoGDI2 (one of the identified protien).
Results: Three differentially expressed proteins were identified. RhoGDI2 and CapG were upregulated, whereas proapoptotic protein Maspin was down-regulated in LoVo/5-FU and validated by Western blotting. Furthermore, knockdown of RhoGDI2 expression by transfection with the RhoGDI2-specific siRNA significantly reduced the resistance to 5-FU in LoVo/5-FU (p < 0.05).
Conclusions: These novel data suggest that these differentially expressed proteins may contribute to the development of 5-FU resistance in colon cancer cells.