地塞米松影响结肠癌细胞对奥沙利铂与氟脲嘧啶化疗敏感性的实验研究  

The Effect of Dexamethasone on the Chemosensitivity of Colon Carcinoma Cells to L-OHP and 5-Fu Treatment

作　　者：周进明[1] 钟大平[1] 周琪[1] 彭秋平[1] 潘凤[1] 何颖 王雪 梁后杰[1] 

机构地区：[1]第三军医大学西南医院肿瘤科,重庆市400038 [2]解放军第521医院肿瘤科

出　　处：《中国肿瘤临床》2010年第3期142-145,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金资助(编号:30171067)~~

摘　　要：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。地塞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 glucocorticoid receptor in human colon cancinoma tissues and cell lines and to explore the survival of colon cancer cell lines treated with dexamethasone alone or in combination with 5-Fu and L-OHP in a way of dexamethasone pretreatment or co-administration in vitro. Methods： The expression of glucocorticoid receptor was detected in 61 cases of colon cancer tissue samples and 4 types of colon cancer cell lines by immunohistochemistry. Apoptosis was detected by Hoechst33342 staining and flow cytometry. MTT assay was employed to detect the chemosensitivity of colon carcinoma cells to L-OHP and 5-Fu with dexamethasone pretreatment for 24 hours or co-administration. Results： Positive GR expression was found in 57.3% colon cancer tissue samples and in Lovo and HCT-116 cell lines, not in HT-29 and SW-480. Apoptosis was detected in GR-expressed Lovo and HCT-116 cells at 72 hours after 1 ×10^-4mol/L Dex treatment, and the rates of apoptosis were higher than those in the control groups without Dex （P〈0.01）, GR-negative cells, HT-29 and SW-480 even treated with 1 × 10^-4mol/L Dex for 72 hours. Pretreatment and co-administration for Lovo cells with 1 × 10^-4mol/L Dex could decrease the IC50 of L-OHP from 13.7±1.31μg/mL to 5.9±0.6μg/mL and 4.8±0.7μg/mL, respectively. IC50 of 5-Fu was decreased from 72.2±8.11μg/mL to 21.1± 4.1 μg/mL and 18.6±4.0μg/mL, respectively. Conclusion： There is expression of glucocorticoid receptor in part of colon carcinoma tissue samples and cell lines. Apoptosis does occur in GR-expressed Lovo and HCT-116cells induced by dexamethasone in vitro. Pretreatment for 24h and co-administiation with Dex can increase the chemosensitivity of Lovo cells to L-OHP and 5-Fu.

关 键 词：结肠癌 糖皮质激素受体 地塞米松 奥沙利铂 氟脲嘧啶 

分 类 号：R735.3[医药卫生—肿瘤]