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Celecoxib Up Regulates the Expression of Drug Efflux Transporter ABCG2 in Breast Cancer Cell Lines.

Kalalinia F, Elahian F, Mosaffa F, Behravan J - Iran J Pharm Res (2014)

Bottom Line: To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines, could be modulated by celecoxib.The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression.Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN. ; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN.

ABSTRACT
Elevated expression of the drug efflux transporter ABCG2 seems to correlate with multidrug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines, could be modulated by celecoxib. The expression of the multidrug resistant gene (ABCG2) at mRNA and protein level was detected by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry analysis, respectively. Among three human breast cancer cell lines ABCG2 and COX-2 were highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression. While celecoxib was able to block the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the expression of ABCG2 up to 4.27 times to the control level at mRNA level and with less intensity at protein level. Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib.

No MeSH data available.


Related in: MedlinePlus

Basal expressions of ABCG2 and COX-2 mRNA in breast cancer cell lines were studied by real time RT-PCR. ABCG2 mRNA level is compared between drug resistant cell line MCF7-MX with MCF-7 (A) and MDA-MB-231 (B) cells. In addition, COX-2 mRNA level is compared between COX-2 overexpressing cell line MDA-MB-231 with MCF- 7 (C) and MCF7-MX (D). Real-time RT-PCR analysis was performed on total RNA extracted from cells. Values were normalized to the β-actin content of samples and expressed as mean ±SD (n = 3).
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Figure 1: Basal expressions of ABCG2 and COX-2 mRNA in breast cancer cell lines were studied by real time RT-PCR. ABCG2 mRNA level is compared between drug resistant cell line MCF7-MX with MCF-7 (A) and MDA-MB-231 (B) cells. In addition, COX-2 mRNA level is compared between COX-2 overexpressing cell line MDA-MB-231 with MCF- 7 (C) and MCF7-MX (D). Real-time RT-PCR analysis was performed on total RNA extracted from cells. Values were normalized to the β-actin content of samples and expressed as mean ±SD (n = 3).

Mentions: In order to assess ABCG2 and COX-2 expression in MCF7 cells, the expression of these two genes was evaluated in MCF7 and control cell lines (MCF7-MX and MDA-MB-231cells) by real time RT-PCR. As shown in Figure 1, ABCG2 mRNA level in resistant cell line MCF7-MX was ≈ 850 and 5200 times more than the ABCG2 mRNA level in MCF-7 and MDA-MB-231 cells, respectively. The expression of COX-2 in MDA-MB-231 cells was ≈ 5.5 and 9.2 times more than MCF-7 and MCF7-MX cells, respectively (Figure 1). These data are further strengthened by the results of flowcytometry analyses for ABCG2 and COX-2 protein expression (data not shown).


Celecoxib Up Regulates the Expression of Drug Efflux Transporter ABCG2 in Breast Cancer Cell Lines.

Kalalinia F, Elahian F, Mosaffa F, Behravan J - Iran J Pharm Res (2014)

Basal expressions of ABCG2 and COX-2 mRNA in breast cancer cell lines were studied by real time RT-PCR. ABCG2 mRNA level is compared between drug resistant cell line MCF7-MX with MCF-7 (A) and MDA-MB-231 (B) cells. In addition, COX-2 mRNA level is compared between COX-2 overexpressing cell line MDA-MB-231 with MCF- 7 (C) and MCF7-MX (D). Real-time RT-PCR analysis was performed on total RNA extracted from cells. Values were normalized to the β-actin content of samples and expressed as mean ±SD (n = 3).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4232806&req=5

Figure 1: Basal expressions of ABCG2 and COX-2 mRNA in breast cancer cell lines were studied by real time RT-PCR. ABCG2 mRNA level is compared between drug resistant cell line MCF7-MX with MCF-7 (A) and MDA-MB-231 (B) cells. In addition, COX-2 mRNA level is compared between COX-2 overexpressing cell line MDA-MB-231 with MCF- 7 (C) and MCF7-MX (D). Real-time RT-PCR analysis was performed on total RNA extracted from cells. Values were normalized to the β-actin content of samples and expressed as mean ±SD (n = 3).
Mentions: In order to assess ABCG2 and COX-2 expression in MCF7 cells, the expression of these two genes was evaluated in MCF7 and control cell lines (MCF7-MX and MDA-MB-231cells) by real time RT-PCR. As shown in Figure 1, ABCG2 mRNA level in resistant cell line MCF7-MX was ≈ 850 and 5200 times more than the ABCG2 mRNA level in MCF-7 and MDA-MB-231 cells, respectively. The expression of COX-2 in MDA-MB-231 cells was ≈ 5.5 and 9.2 times more than MCF-7 and MCF7-MX cells, respectively (Figure 1). These data are further strengthened by the results of flowcytometry analyses for ABCG2 and COX-2 protein expression (data not shown).

Bottom Line: To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines, could be modulated by celecoxib.The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression.Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN. ; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN.

ABSTRACT
Elevated expression of the drug efflux transporter ABCG2 seems to correlate with multidrug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines, could be modulated by celecoxib. The expression of the multidrug resistant gene (ABCG2) at mRNA and protein level was detected by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry analysis, respectively. Among three human breast cancer cell lines ABCG2 and COX-2 were highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression. While celecoxib was able to block the 12-O-tetradecanoylphorbol-13-acetate (TPA)-mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the expression of ABCG2 up to 4.27 times to the control level at mRNA level and with less intensity at protein level. Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib.

No MeSH data available.


Related in: MedlinePlus