PPARγ在胃癌的表达及曲格列酮对胃癌SGC7901细胞生长的影响  

Study on the expression of PPARγ and effects of TGZ on the growth of SGC7901 gastric carcinoma cell line

作　　者：崔涛[1] 刘莹[1] 朱祖安[2] 刘霞[3] 

机构地区：[1]徐州医学院病理学教研室,江苏徐州221004 [2]徐州医学院附属医院消化内科,江苏徐州221002 [3]徐州市中心医院病理科,江苏徐州221009

出　　处：《徐州医学院学报》2009年第3期144-148,共5页Acta Academiae Medicinae Xuzhou

基　　金：江苏省高校自然科学基金(05KJD320234);徐州市科技局资助项目(06-34)

摘　　要：目的探讨过氧化物酶体增殖物活化受体γ(PPARγ)在胃癌及癌前病变中的表达,研究PPARγ激动剂曲格列酮(troglitazone,TGZ)对人胃癌细胞SGC7901生长抑制作用及其作用机制。方法免疫组织化学方法检测PPARγ在胃癌及癌前病变中的表达;体外培养SGC7901细胞给予TGZ干预,四甲基偶氮唑蓝(MTT)法、流式细胞术、苏木精-伊红染色、免疫细胞化学方法、Western blot检测TGZ作用后SGC7901细胞生长情况、凋亡率及细胞周期的改变、细胞形态学变化、PPARγ表达情况。结果①免疫组化染色结果显示在轻度不典型增生、重度不典型增生及胃癌标本中PPARγ阳性表达率为15.15%(5/33)、66.67%(14/21)、71.43%(60/84),轻度不典型增生与重度不典型增生及胃癌组间有统计学差异(P<0.05)。②体外实验结果显示SGC7901细胞与不同浓度的TGZ共同培养,细胞的生长受到不同程度的抑制,TGZ 50μmol/L组与对照组相比P<0.05,同时其作用具有浓度及剂量依赖性,苏木精-伊红染色结果显示实验组肿瘤细胞的生长较阴性对照组逐渐稀疏,出现细胞体积变小、形态不规则、细胞皱缩、核固缩、胞浆空泡等形态学表现。免疫组织化学染色显示PPARγ在SGC7901细胞中有较高表达,50μmol/L与阴性对照组及低浓度25μmol/L组相比P<0.05,流式细胞仪检测结果显示TGZ 25μmol/L组起作用72 h后,细胞凋亡率明显升高,处于G0/G1与S期的细胞比例与阴性对照组相比,具有统计学意义(P<0.05)。Western blot结果显示TGZ作用72 h后与阴性对照组相比,高浓度50μmol/L组PPARγ表达增加(P<0.01)。结论应用TGZ可以将SGC7901细胞阻滞于G0/G1期,进而抑制其增殖。Objective To explore the expression of peroxisome proliferator - activated receptor γ （PPARγ） in gas- tric carcinoma and precancerous lesions and to investigate the inhibitory effects and mechanisms of TGZ, a PPARγ agonist on human gastric carcinoma cell line SCC7901. Methods 1. The expression of PPARγ protein in gastric precancerous and cancerous lesions was determined using immunohistochemical assays （PowerVisionTM two - step method ）. 2. SCC7901 cells cultured in vitro were treated with TGZ for intervention. MTT assay, flow cytometry, hematoxylin -cosine （H -E） staining, immunohistochemical assays and Western blotting were used to detect the morphological changes, the effects on the growth, apoptosis and the cycle progression and the expression of PPARγ of the human tumor SGC7901 ceils, respectively. Results 1. The expressions of PPARγ were 15.15% （5/33）, 66.67% （ 14/21 ） and 71.43% （60/84） in low grade atypical hyperplasia, high grade atypical hyperplasia and gastric carcinoma specimens, The differ- ences were statistically significant （ P 〈 0.05 ）. 2. The in vitro experiment revealed the inhibited growth of SGC7901 cells cultured with TGZ at the concentration of 50μmol/L, in a concentration - and dose -dependent manner, compared with the control group （P 〈 0.05 ）. H - E staining showed that the SCC7901 cells were sparser, with such morphological man- ifestations as diminished cell sizes, morphological irregularity, cell shrinkage, karyopycnosis and cytoplasmic vacuoles,etc. Immunohistochemieal staining revealed an upregu/ated expression level of PPARγ in the SGC7901 cells, compared with the negative control group and the low concentration （25 μmol/L） group （P 〈 0.05 ）. Flow cytometry detection showed that the apoptotic rate of the tumor cells markedly increased 72 hours after 25μmol/L TGZ treatment, with the tumor cells arrested in G0/G1 phase and reduced in S phase, compared with the negative control group （ P 〈 0.05 ）, Western blot detection sho

关 键 词：过氧化物酶体增殖物活化受体Γ SGC7901胃癌细胞 曲格列酮 

分 类 号：R735.2[医药卫生—肿瘤]