目的:检测糖皮质激素受体在结肠癌组织及细胞株中的表达,探讨地塞米松共处理或预处理24h,结肠癌细胞株对奥沙利铂和氟脲嘧啶化疗敏感性的变化.方法:采用免疫组化检测糖皮质激素受体在61例结肠癌组织标本及4种结肠癌细胞株中的表达;Hoechst33342染色、流式细胞仪检测体外地塞米松对结肠癌细胞株的凋亡诱导作用;以MTT法检测地塞米松共处理或预处理24h后.结肠癌Lovo细胞株对奥沙利铂和氟脲嘧啶化疗敏感性的变化.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仅Lovo和HCT-116表达糖皮质激素受体,HT-29和SW-480细胞不表达.单独应用地塞米松后,对糖皮质激素受体阳性的Lovo和HCT-116细胞有较强的促凋亡作用,对不表达糖皮质激素受体的HT-29和SW-480细胞作用则不明显.以1×10~(-4)mol/L的地塞米松处理Lovo细胞24h,或与奥沙利铂共处理可使奥沙利铂的IC50从(13.7±1.3)μg/mL降低至(5.9±0.6)μg/mL和(4.8±0.7)μg/mL;同样处理可使氟脲嘧啶的IC50从(72.2±8.1)μg/mL降低至(21.1±4.1)μg/mL和(18.6±4.0)μg/mL.结论:部分结肠癌组织及细胞株表达糖皮质激素受体.地基米松体外作用能够促进糖皮质激素受体阳性的结肠癌细胞发生凋亡,与奥沙利铂和氟脲嘧啶预处理或共处理后可以增加结肠癌细胞的化疗敏感性.
OBJECTIVE:To examine the expression of the glucocorticoid receptor and the effect on proliferation and apoptosis induced by Dexamethasone in human colon carcinoma cell lines Lovo, HCT-116,HT-29 and SW-480 in vitro. METHODS: GR protein was determined by immunohistochemistry and GR mRNA by RT-PCR. Proliferation and apoptosis were detected by MTT, DNA Ladder method and flow cytometer. RESULTS: The glucocorticoid receptor was determined in Lovo and HCT-116, not in HT-29 and SW-480. Dexamethasone had an inhibitory effect on the four human colon cancer cell lines, respectively, and Lovo and HCT-116 cells were among the most sensitive. And the characteristic apoptotic DNA Ladders of Lovo were confirmed by DNA Ladder method. Apoptosis cusps were investigated by flow cytometer in Lovo and HCT-116, the rates of apoptosis [Lovo(34.8±1.9)% and HCT-116(33.6±1.4)%] were higher than those [Lovo(2.9±0.4)% and HCT-116(6.4±1.3)%] in the control groups without Dex. CONCLUSION: The results demonstrate expression of the glucocorticoid receptor in Lovo and HCT-116. Inhibiton of proliferation and apoptosis occur on Lovo and HCT-116 cells induced by dexamethasone in vitro, which may have some relationship with glucocorticoid receptor.