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

Nie F, Cao J, Tong J, Zhu M, Gao Y, Ran Z - J. Biomed. Sci. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. niefang7@163.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

The effect of RKIP gene on invasiveness of cells: Significantly higher number of invasive cells in SW1116 /RKIP− cells with RKIP down-regulation, as compared to SW1116 control cells (P <0.05); Decreased number of invasive cells in LoVo PEBP-1 compared to LoVo con (P <0.05). Abbreviations: RKIP, Raf kinase inhibitor protein; LoVo PEBP-1, LoVo cells transfected with over-expression vector pIRES2-EGFP/PEBP-1; LoVo con, LoVo control cells
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Fig5: The effect of RKIP gene on invasiveness of cells: Significantly higher number of invasive cells in SW1116 /RKIP− cells with RKIP down-regulation, as compared to SW1116 control cells (P <0.05); Decreased number of invasive cells in LoVo PEBP-1 compared to LoVo con (P <0.05). Abbreviations: RKIP, Raf kinase inhibitor protein; LoVo PEBP-1, LoVo cells transfected with over-expression vector pIRES2-EGFP/PEBP-1; LoVo con, LoVo control cells

Mentions: Under the same culture conditions and inoculation density, the down-regulation of RKIP in SW1116/RKIP— increased the number of migrated cells on the lower surface of the matrigel-coated transwell membrane (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.01) at 72 h. The up-regulation of RKIP in LoVo cells transfected with pIRES2-EGFP/PEBP-1 reduced the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05) at 72 h (Fig. 5). There were no cell across the membrane at 24 h, and only few cells were found across it in both the groups at 48 h.Fig. 5


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

Nie F, Cao J, Tong J, Zhu M, Gao Y, Ran Z - J. Biomed. Sci. (2015)

The effect of RKIP gene on invasiveness of cells: Significantly higher number of invasive cells in SW1116 /RKIP− cells with RKIP down-regulation, as compared to SW1116 control cells (P <0.05); Decreased number of invasive cells in LoVo PEBP-1 compared to LoVo con (P <0.05). Abbreviations: RKIP, Raf kinase inhibitor protein; LoVo PEBP-1, LoVo cells transfected with over-expression vector pIRES2-EGFP/PEBP-1; LoVo con, LoVo control cells
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4502602&req=5

Fig5: The effect of RKIP gene on invasiveness of cells: Significantly higher number of invasive cells in SW1116 /RKIP− cells with RKIP down-regulation, as compared to SW1116 control cells (P <0.05); Decreased number of invasive cells in LoVo PEBP-1 compared to LoVo con (P <0.05). Abbreviations: RKIP, Raf kinase inhibitor protein; LoVo PEBP-1, LoVo cells transfected with over-expression vector pIRES2-EGFP/PEBP-1; LoVo con, LoVo control cells
Mentions: Under the same culture conditions and inoculation density, the down-regulation of RKIP in SW1116/RKIP— increased the number of migrated cells on the lower surface of the matrigel-coated transwell membrane (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.01) at 72 h. The up-regulation of RKIP in LoVo cells transfected with pIRES2-EGFP/PEBP-1 reduced the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05) at 72 h (Fig. 5). There were no cell across the membrane at 24 h, and only few cells were found across it in both the groups at 48 h.Fig. 5

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. niefang7@163.com.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus