Open Access

Celecoxib increases retinoid sensitivity in human colon cancer cell lines

  • Jian-Pei Liu1,
  • Hong-Bo Wei1Email author,
  • Zong-Heng Zheng1,
  • Wei-Ping Guo1 and
  • Jia-Feng Fang1
Cellular & Molecular Biology LettersAn International Journal201015:16

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

Received: 26 August 2009

Accepted: 17 May 2010

Published: 24 May 2010

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.

Key words

Colonic neoplasm Retinoic acid Celecoxib Sensitivity

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