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目的:观察结肠癌组织糖皮质激素受体表达及地塞米松(dexamethasone,Dex)体外对结肠癌细胞的作用,探讨糖皮质激素受体β(GRβ)亚型表达在结肠癌细胞激素反应中的作用。方法:免疫组化检测GR在结肠癌组织和细胞株中的表达,MTT和annexinⅤ-FITC/PI双染检测糖皮质激素对结肠癌细胞的作用,RT-PCR检测糖皮质激素作用过程中GRα和GRβ的mRNA表达变化,si RNA沉默GRβ的表达对细胞激素敏感性的影响。结果:在57.3%的结肠癌组织标本中糖皮质激素受体呈阳性表达,在四种结肠癌细胞株中只有LoVo和HCT116表达糖皮质激素受体,HT29和SW480细胞不表达。在体外实验中地塞米松对糖皮质激素受体阳性的LoVo和HCT116细胞有较强的增殖抑制和促凋亡作用;在Dex作用过程中GRα和GRβ表达均升高,但是GRβ升高更明显;转染GRβ的小分子干扰片断后,Lo-Vo细胞GRβ的mRNA表达下降67.3%,Dex诱导的细胞凋亡率则从(34.7±1.8)%上升至(45.4±4.3)%(P<0.05)。结论:糖皮质激素对结肠癌细胞有增殖抑制和凋亡诱导作用,细胞GRβ表达增加抑制结肠癌细胞对糖皮质激素的敏感性。
OBJECTIVE: To observe the effect of dexamethasone (Dex) on the expression of glucocorticoid receptor in colon cancer and the effect of dexamethasone (Dex) on colon cancer cells in vitro and to investigate the expression of glucocorticoid receptor β (GRβ) subtypes in hormone responses of colon cancer cells effect. Methods: The expression of GR in colorectal cancer tissues and cell lines was detected by immunohistochemistry. The effects of glucocorticoid on colon cancer cells were detected by MTT assay and annexinⅤ-FITC / PI double staining. The expression of GRα GRβ mRNA expression changes, si RNA silencing GRβ expression on cytokine sensitivity. RESULTS: Glucocorticoid receptor was expressed in 57.3% of colon cancer specimens. Only LoVo and HCT116 expressed glucocorticoid receptor in four colon cancer cell lines, but not in HT29 and SW480 cells. In vitro, dexamethasone exerted strong inhibitory and proapoptotic effects on glucocorticoid receptor-positive LoVo and HCT116 cells. The expression of GRα and GRβ increased during Dex treatment, but GRβ increased more significantly The mRNA expression of GRβ in Lo-Vo cells decreased by 67.3% and the apoptosis rate induced by Dex increased from (34.7 ± 1.8)% to (45.4 ± 4.3)% (P <0.05) after transfected with small interfering fragments of GRβ ). CONCLUSION: Glucocorticoid can inhibit the proliferation and induce the apoptosis of colon cancer cells. The increased expression of GRβ inhibits the sensitivity of colon cancer cells to glucocorticoid.