罗格列酮对胃癌AGS细胞株生长的影响  

Effects of PPARγ ligand rosiglitazone on AGS gastric cancer cells growth

作　　者：陈白莉[1] 柯春龙[2] 何瑶[1] 曾志荣[1] 梁伟强[3] 于君[3] 胡品津[1] 

机构地区：[1]中山大学附属第一医院消化内科,广东广州510080 [2]中山大学附属第一医院神经外科,广东广州510080 [3]香港中文大学消化疾病研究所及李嘉诚健康研究所

出　　处：《中国医师杂志》2009年第10期1314-1317,共4页Journal of Chinese Physician

基　　金：基金项目：广东省医学科研基金资助项目（A2008175）

摘　　要：目的探讨PPARγ配体罗格列酮对胃癌AGS细胞株增殖、凋亡的作用及其分子机制。方法采用MTS法测定罗格列酮对胃癌AGS细胞株存活率的影响，流式细胞术检测罗格列酮对AGS细胞凋亡的影响，荧光定量PCR及Western blot法检测罗格列酮对PPARγ、HCaRG及DLK1 mRNA及蛋白的表达。结果不同浓度罗格列酮（1—100μM）处理AGS细胞株24h及48h，细胞的存活率明显降低，其作用呈浓度及时间依赖性，预先加入PPARγ拮抗剂GW9662可部分逆转罗格列酮的作用；不同浓度罗格列酮处理AGS细胞株48h，细胞凋亡百分率明显高于对照组（t≥2．97，P〈0．05），GW9662不能逆转罗格列酮的作用；罗格列酮诱导AGS细胞株PPARγ、HCaRG及DLK1的表达，并呈剂量依赖，GW9662能阻断罗格列酮诱导DLK1表达的作用，而不能阻断其诱导HCaRG表达的作用。结论罗格列酮通过PPARγ依赖及非依赖两种途径抑制胃癌AGS细胞株生长，诱导DLK1及HCaRG表达可能是罗格列酮抗胃癌作用机制之一。Objective To investigated the effects of PPARγ ligand rosiglitazone on cell viability and apoptosis in AGS gastric cancer cell line and determine the possible mechanisms of rosiglitazone. Methods MTS method was used to measure the cell viability, flow cytometry analysis was used to measure apoptosis. The PPARγ, HCaRG, DLK1 mRNA and protein was examined by real-time PCR and western blot. Results The cell viability of AGS cells treated with rosiglitazone was decreased in concentration- and time-dependent manner. Preincubation with irreversible PPARγ antagonist GW9662 partly reversed the decrease of the cell viability induced by rosiglitazone. After treating apoptosis in AGS cells induced by different concentration rosiglitazone, the percentage of apoptosis was higher than those in control group. Preincubation with GW9662 cannot reverse the increase of the cell apoptosis induced by rosiglitazone. Rosiglitazone markedly induced the expression of PPARγ, HCaRG, and DLKI in AGS cell line. Pre-treatment with GW9662 markedly reduced rosiglitazone - induced PPARγ and DLK1 expression, but could not block HCaRG expression. Conclusion Rosiglitazone suppressed AGS cells growth via PPARγ-dependent and -independent pathway. Upregulation of HCaRG and DLK1 may be one of the mechanisms underlying the anticancer effect of rosigltizaone in gastric cancer.

关 键 词：噻唑烷二酮类/药理学 胃肿瘤/药物疗法 细胞增殖 细胞凋亡 PPARγ/代谢 基因表达 

分 类 号：R735[医药卫生—肿瘤]