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Kim, Park, Nam, and Bae: Synergistic effects of sorafenib and celecoxib inhibit growth and VEGF expression in Hec-1A endometrial cancer cell line
Original Article
Korean Journal of Obstetrics & Gynecology

Korean Journal of Obstetrics & Gynecology 2012; 55(11): 814-821.

Published online: 16 November 2012

DOI: https://doi.org/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

Jeong Sig Kim, MD1, Bo Ra Park, MD1, Gye Hyun Nam, MD2, Dong Han Bae, MD3

1Department of Obstetrics and Gynecology, Soonchunhyang Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Korea.

2Department of Obstetrics and Gynecology, Soonchunhyang Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

3Department of Obstetrics and Gynecology, Soonchunhyang Cheonan Hospital, Soonchunhyang University College of Medicine, Cheonan, Korea.

Corresponding author: Jeong Sig Kim, MD. Department of Obstetrics and Gynecology, Soonchunhyang Seoul Hospital, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 140-743, Korea. Tel: +82-2-709-9337, Fax: +82-2-709-9332, jskim@schmc.ac.kr

Received 9 August 2012       Revised 18 September 2012       Accepted 18 September 2012

Copyright © 2012. Korean Society of Obstetrics and Gynecology

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 µmol/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.

Keywords: Endometrial cancer, Sorafenib, Celecoxib, Vascular endothelial growth factor

Figures and Tables

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.
kjog-55-814-g001
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.
kjog-55-814-g002

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