塞来昔布抑制胃癌多药耐药基因表达的研究
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黄雯雯 E-mailhuang_wen_wen1975@163.com

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Selective cyclooxygenase-2 inhibitor down-regulates the expression of multidrug resistance gene in gastric cancer cells
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    摘要:

    目的:探讨选择性环氧合酶 (COX-2)抑制剂塞来昔布对胃癌细胞株BGC823多药耐药(MDR)1表达的影响。
    方法:BGC823细胞株经不同浓度的塞来昔布处理后,用ELISA法检测胃癌细胞前列腺素E2(PGE2)的分泌;24,48 h后用RT-PCR检测多药耐药MDR1 mRNA的表达,48 h后用免疫细胞化学染色法检测P-gp的表达。
    结果:塞来昔布可显著抑制胃癌细胞株BGC823的PGE2分泌,并呈浓度依赖性(P<0.05)。不同浓度塞来昔布作用于细胞后,胃癌细胞株BGC823的MDR/P-gp表达受不同程度抑制,100 μmol/L的塞来昔布对MDRl mRNA表达抑制作用强于10 μmol/L (P<0.01)。作用48 h与24 h相比,塞来昔布对MDRl mRNA 表达的抑制作用更强(P<0.01)。
    结论:塞来昔布可抑制BGC823 MDR1/P-gp的表达,且呈量效关系。其可能通过抑制COX-2活性而抑制PGE2表达,最终抑制P-gp的表达。

    Abstract:

    Objective:To investigate the effect of celecoxib, a selective cyclooxygenase-2 inhibitor, to down-regulate the expression of multidrug resistance (mdrl) gene in the gastric cancer cell BGC823.
    Methods:BGC823 cells were treated with celecoxib in different concentrations (0,10μmol/L and 100μmol/L) respectively.Prostaglandin E2 (PGE2) was detected by ELISA. Twenty four hs and 48 hs later,the expression of mdrl mRNA were detected by RT-PCR. P-gp protein expression in BGC823 cells was detected by immunocytochemical technique after celecoxib treatment.
    Results:Celecoxib inhibited the expression of PGE2 in a dose dependent manner(P<0.05,P<0.01).Same effective situation between the concentration was found on the P-gp expression during the treatment with celecoxib; while the expression of mdrl mRNA  was down regulated more effectively after 48 h treatment when compared to that in 24 hs treatment group(P<0.01).
    Conclusions:Celecoxib can inhibit the expression of mdrl/P-gp in a time and dose dependent manner, which is likely to be through inhibiting COX-2 activity.The results suggest that a selective COX-2 inhibitor may play a potential role in overcoming the chemotherapeutic resistance of gastric cancer cells.

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黄雯雯.塞来昔布抑制胃癌多药耐药基因表达的研究[J].中国普通外科杂志,2010,19(10):1076-1079.
DOI:10.7659/j. issn.1005-6947.2010.10.006

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  • 收稿日期:2009-11-07
  • 最后修改日期:2010-06-02
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  • 在线发布日期: 2010-10-15