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Celecoxib increases retinoid sensitivity in human colon cancer cell lines

Cellular & Molecular Biology Letters volume 15, pages 440–450 (2010)Cite this article

Abstract

Retinoid resistance has limited the clinical application of retinoids as differentiation-inducing and apoptosis-inducing drugs. This study was designed to investigate whether celecoxib, a selective COX-2 inhibitor, has effects on retinoid sensitivity in human colon cancer cell lines, and to determine the possible mechanism of said effects. Cell viability was measured using the MTT assay. Apoptosis was detected via Annexin-V/PI staining and the flow cytometry assay. PGE2 production was measured with the ELISA assay. The expression of RARβ was assayed via western blotting. The results showed that celecoxib enhanced the inhibitory effect of ATRA in both COX-2 high-expressing HT-29 and COX-2 low-expressing SW480 cell lines. Further study showed the ATRA and celecoxib combination induced greater apoptosis, but that the addition of PGE2 did not affect the enhanced growth-inhibitory and apoptosis-inducing effects of the combination. Moreover, NS398 (another selective COX-2 inhibitor) did not affect the inhibitory effects of ATRA in the two cell lines. Western blotting showed that the expression of RARβ in HT-29 cell lines was increased by celecoxib, but not by NS398, and that the addition of PGE2 did not affect the celecoxib-induced expression of the retinoic acid receptor beta. In conclusion, celecoxib increased the expression of RARβ and the level of cellular ATRA sensitivity through COX-2-independent mechanisms. This finding may provide a potential strategy for combination therapy.

Abbreviations

ATRA:

all-trans retinoic acid

COX-2:

Cycloxygenase-2

4HPR:

N-(4-hydroxyphenyl) retinamide

MTT:

methyl thiazolyl tetrazolium

PGE2 :

prostaglandin E2

RARβ:

retinoic acid receptor beta

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Authors and Affiliations

  1. Department of Gastrointestinopancreatic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Tian He Road 600, Guangzhou, 510630, P.R. China

    Jian-Pei Liu, Hong-Bo Wei, Zong-Heng Zheng, Wei-Ping Guo & Jia-Feng Fang

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  1. Jian-Pei Liu
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  2. Hong-Bo Wei
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Correspondence to Hong-Bo Wei.

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Liu, JP., Wei, HB., Zheng, ZH. et al. Celecoxib increases retinoid sensitivity in human colon cancer cell lines. Cell Mol Biol Lett 15, 440–450 (2010). https://doi.org/10.2478/s11658-010-0016-2

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  • DOI: https://doi.org/10.2478/s11658-010-0016-2

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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