Korean J Obstet Gynecol.  2012 Nov;55(11):814-821. 10.5468/KJOG.2012.55.11.814.

Synergistic effects of sorafenib and celecoxib inhibit growth and VEGF expression in Hec-1A endometrial cancer cell line

• Kim JS
• Park BR
• Nam GH
• Bae DH

• KMID: 2274149
• DOI: http://doi.org/10.5468/KJOG.2012.55.11.814

Abstract

OBJECTIVE
The aim of this study was to investigate whether combination of sorafenib and celecoxib exhibited an anti-tumor efficacy or altered expression of vascular endothelial growth factor (VEGF) in Hec-1A endometrial cancer cell line.
METHODS
To determine whether sorafenib or celecoxib-induced growth inhibition was determined by the (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay. Expression of VEGF and p53 were evaluated using the reverse transcription polymerase chain reaction.
RESULTS
Combination of sorafenib 10 ng/mL and celecoxib 50 micromol/L exhibited synergistic inhibitory effects compared to treatment with each agent alone (P<0.0001). VEGF expression was also down regulated after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib in Hec-1A cells. However, there was no alteration of p53 expression in Hec-1A cells after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib.
CONCLUSION
Combination treatment of sorafenib and celecoxib to Hec-1A endometrial cancer cell line revealed the ability to inhibit growth and expression of VEGF.

Keyword

Endometrial cancer; Sorafenib; Celecoxib; Vascular endothelial growth factor

MeSH Terms

Cell Line
Endometrial Neoplasms
Female
Niacinamide
Phenylurea Compounds
Pyrazoles
Reverse Transcription
Sulfonamides
Vascular Endothelial Growth Factor A
Niacinamide
Phenylurea Compounds
Pyrazoles
Sulfonamides
Vascular Endothelial Growth Factor A

Figure

• 

  Fig. 1 (A) Viability of Hec-1A cells treated with 5 ng/mL, 10 ng/mL, 20 ng/mL, and 50 ng/mL of sorafenib after 24 hours of treatment. Cell growth was inhibited by sorafenib treatment in a concentration-dependent manner. Significant differences are indicated by (aP<0.0001 vs. control condition). (B) Viability of Hec-1A cells treated with celecoxib in rising concentrations between 20 µmol/L and 100 µmol/L after 24 hours of treatment. Significant differences are indicated by (aP<0.0001 vs. nontreated control). (C) Viability of Hec-1A cells treated with sorafenib 10 ng/mL, celecoxib 50 µmol/L or in combination with sorafenib 10 ng/mL and celecoxib 50 µmol/L. aP<0.0001 when compared with cells under 'sorafenib 10 + celecoxib 50' conditions.

• 

  Fig. 2 (A) Expression of vascular endothelial growth factor (VEGF) in Hec-1A cells after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib. Endometrial cancer cell line was treated with sorafenib and/or celecoxib for indicated concentrations. β-actin was used as a control for protein loading. (B) Expression of p53 in Hec-1A cells after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib. Endometrial cancer cell line was treated with sorafenib and/or celecoxib for indicated concentrations. β-actin represents the loading control. 24 hours: 1, control; 2, sorafenib 10 ng/mL; 3, sorafenib 10 ng/mL + celecoxib 100 µmol/L; 4, sorafenib 100 ng/mL + celecoxib 100 µmol/L; 72 hours: 5, control; 6, sorafenib 10 ng/mL; 7, sorafenib 10 ng/mL + celecoxib 100 µmol/L; 8, sorafenib 100 ng/mL + celecoxib 100 µmol/L.

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