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环氧合酶-2诱导人胃腺癌细胞系SGC7901中P-糖蛋白表达的机制

Mechanism of P-glycoprotein expression in the SGC7901 human gastric adenocarcinoma cell line induced by cyclooxygenase-2.

作者信息

Gu Kang-Sheng, Chen Yu

机构信息

Department of Oncology, the Fist Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Asian Pac J Cancer Prev. 2012;13(5):2379-83. doi: 10.7314/apjcp.2012.13.5.2379.

Abstract

OBJECTIVE

To investigate possible signal pathway involvement in multi-drug resistant P-glycoprotein (P-gp) expression induced by cyclooxygenase-2 (COX-2) in a human gastric adenocarcinoma cell line stimulated with pacliaxel (TAX).

METHODS

The effects of TAX on SGC7901 cell growth with different doses was assessed by MTT assay, along with the effects of the COX-2 selective inhibitor NS-398 and the nuclear factor-KB (NF-KB) pathway inhibitor pyrrolidine dithiocarbamate (PDTC). Influence on COX-2, NF-KB p65 and P-gp expression was determined by Western blotting.

RESULTS

TAX, NS-398 and PDTC all reduced SGC7901 growth, with dose- dependence. With increasing dose of TAX, the expression of COX-2, p65 and P-gp showed rising trends, this being reversed by NS-398. PDTC also caused decrease in expression of p65 and P-gp over time.

CONCLUSION

COX-2 may induce the expression of P-gp in SGC7901 cell line via the NF-kappa B pathway with pacliaxel stimulation.

摘要

目的

研究在紫杉醇(TAX)刺激的人胃腺癌细胞系中,环氧化酶-2(COX-2)诱导多药耐药P-糖蛋白(P-gp)表达可能涉及的信号通路。

方法

采用MTT法评估不同剂量TAX对SGC7901细胞生长的影响,以及COX-2选择性抑制剂NS-398和核因子-κB(NF-κB)通路抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)的影响。通过蛋白质免疫印迹法测定对COX-2、NF-κB p65和P-gp表达的影响。

结果

TAX、NS-398和PDTC均呈剂量依赖性降低SGC7901细胞的生长。随着TAX剂量的增加,COX-2、p65和P-gp的表达呈上升趋势,NS-398可使其逆转。随着时间的推移,PDTC也导致p65和P-gp的表达下降。

结论

在紫杉醇刺激下,COX-2可能通过NF-κB通路诱导SGC7901细胞系中P-gp的表达。

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