摘要
目的:研究亚细胞毒性剂量As2O3对rhTRAIL诱导胃癌细胞凋亡的影响及其机制.方法:人胃腺癌细胞株SGC 7901以As2O3(1μmol/L),rhTRAIL(500μg/L)及两者联用处理:采用AnnexinV-FITC和PI双染色流式细胞仪检测细胞凋亡:用间接免疫荧光染色结合流式细胞技术检测细胞表面TRAIL R1/DR4和TRAIL R2/DR5分子表达;RT-PCR方法检测TRAIL R1/DR4和TRAIL R2/DR5 mRNA表达.结果:rhTRAIL在单用或与As2O3联用时均可以诱导胃癌SGC7901细胞凋亡,并且随着作用时间延长(12-72 h),细胞凋亡率逐渐增高.As2O3与rhTRAIL联用24,48,72 h后,SGC7901细胞凋亡率分别显著高于单用rhTRAIL处理相同时间细胞(36.49%±7.12%,47.13%±3.44%,55.63%±7.16%vs 29.78%±3.18%、38.56%±1.89%,43.12%±6.23%,P<0.05); As2O3单用或联用rhTRAIL处理SGC7901细胞24 h后,细胞表面TRAIL R1/DR4和TRAIL R2/DR5分子的平均荧光密度(MFI)较对照组细胞显著增加(R1/DR4:29.44±4.29,26.14±3.40 vs13.45±3.81,P<0.05或P<0.01;R2/DR5:28.04±0.79.3 1.47±4.56vs16.45±5.07,P<0.05或P<0.01);与此同时,TRAIL R1/DR4和TRAIL R2/DR5mRNA表达水平增高.结论:亚细胞毒性剂量As2O3可能通过增加TRAIL R1/DR4和TRAIL R2/DR5基因表达、上调细胞表面TRAIL死亡受体从而增加胃癌细胞SGC7901对rhTRAIL的敏感性,两药可能联合用于治疗胃癌.
AIM: To investigate the effects of subcytotoxic concentration of arsenic trioxide (As203) on the rhTRAIL-induced apoptosis in SGC7901 cells and its related mechanism.
METHODS: The human gastric cancer cell line SGC7901 was treated with AS203 (1 μmol/L), rhTRAIL (500 μg/L), respectively, or in combination. The cell apoptosis was detected by flow cytometry (AnnexinV-FITC-PI assay); the expression of TRAIL R1/DR4 and TRAIL R2/DR5 on the cell surface were determined by indirect fluorescence staining and flow cytornetry; the expression of TRAIL R1/DR4 and TRAIL R2/DR5 mRNA was determined by reverse transcriptionpolymerase chain reaction (RT-PCR). RESULTS: Used along or in combination with As2O3, rhTRAIL induced apoptosis of SGC7901 cells in a time-dependent manner (12-72 h). After being exposed to rhTRAIL in combination with As203 for 24, 48 and 72 h, the apoptosis rates of SGC7901 cells were significantly higher than those of cells treated with the same concentration of rhTRAIL alone (36.49% ± 7.12%, 47.13% ± 3.44%, 55.63% ± 7.16% vs 29.78% ± 3.18%, 38.56%± 1.89%, 43.12% ± 6.23%, respectively, P〈 0.05). AS2O3, used along or in combination with rhTRAIL (500μg/L) for 24 h, increased the expression of TRAIL R1/DR4 and TRAIL R2/DR5 on the cell surface significantly (R1/DR4:29.44 ± 4.29, 26.14 ± 3.40 vs 13.45 ± 3.81, P 〈 0.05) R2/ DR5: 28.04 ± 0.79, 31.47 ± 4.56 vs 16.45 ± 5.07, P 〈 0.05), and at the same time, increased the mRNA levels of the two receptors.
CONCLUSION: Subcytotoxic concentration of AS2O3 can sensitize SGC7901 cells to rhTRAIL through up-regulation of TRAIL R1/DR4 and TRAIL R2/DR5 on cell surface and their mRNA levels. Combination of rhTRAIL and AS203 can be used in the therapy of gastric cancer.
出处
《世界华人消化杂志》
CAS
北大核心
2006年第27期2679-2683,共5页
World Chinese Journal of Digestology
关键词
肿瘤坏死因子相关的凋亡诱导配体
三氧化二砷
胃癌
凋亡
Tumor necrosis factor-related apoptosisinducing ligand
Arsenic trioxide
Gastric carcinoma
Apoptosis