Role of Raf-kinase inhibitor protein in colorectal cancer and its regulation by hydroxycamptothecine

Journal of Biomedical Science

Zhihua Ran²  Yuan Gao¹  Mingming Zhu²  Jinlu Tong²  Jianguo Cao¹  Fang Nie¹ 

[1] Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai 200001, China

关键词: Raf-kinase inhibitor protein;    Role;    Hydroxycamptothecine;    Colorectal cancer;   

Others  :  1219610
DOI  :  10.1186/s12929-015-0162-y

 received in 2014-11-13, accepted in 2015-07-02,  发布年份 2015

【 摘 要 】

Background

Recently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity.

Results

Immunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine.

Conclusions

RKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT.

【 授权许可】

   
2015 Nie et al.

【 图 表 】

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