活化的过氧化物酶体增生物激活受体-γ诱导人类肺癌细胞凋亡及其机制的研究  

Apoptosis of human lung cancer cells induced by activated peroxisome proliferator-activated receptor-γ and its mechanism

作　　者：张敏[1] 邹萍[1] 白明[2] 陶晓南[2] 金阳[2] 郭荣[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院血液病研究所,武汉430022 [2]华中科技大学同济医学院附属协和医院呼吸科,武汉430022

出　　处：《中华医学杂志》2003年第13期1169-1172,共4页National Medical Journal of China

基　　金：湖北省自然科学基金资助项目 (98J10 2 )

摘　　要：目的　探讨配体活化的过氧化物酶体增生物激活受体 (PPAR) γ对人肺癌细胞生长的影响及其机制。方法　以逆转录聚合酶链反应和Western印迹法分别检测肺癌细胞系上PPAR γ的表达 ,以四甲基偶氮唑盐微量酶反应比色 (MTT)法检测经PPAR γ的配体作用后的细胞增殖情况 ,以TUNEL检测PPAR γ的配体作用后的细胞凋亡情况 ,以原位杂交和免疫组化检测处理前后bax和bcl 2的mRNA和蛋白质水平的变化 ,并以免疫组化检测处理前后细胞半胱氨蛋白水解酶 3的表达情况。结果　肺癌细胞系上有PPAR γ的表达 ,经配体活化后能明显抑制细胞生长 ,且与时间和剂量有关 ;配体活化后的PPAR γ能诱导细胞凋亡 ,且半胱氨蛋白水解酶 3与bax、bcl 2在诱导凋亡前后均有增加 ,与凋亡程度呈正相关 ,但bax/bcl 2比值在凋亡前后亦增加。结论　PPAR γ经配体活化后能通过诱导凋亡而抑制肺癌细胞的生长 ,且bax/bcl 2的比值与半胱氨蛋白水解酶 3在此过程中起作用 ,因此该受体在肺癌的发病及进展中起重要作用 ,有可能成为未来肺癌治疗的新靶点。Objective To explore the effects of peroxisome proliferator-activated receptor-γ (PPAR-γ) on the growth of human lung cancer cell lines and its possible mechanism. Methods Human non-small cell lung cancer (NSCLC) cells of the A549 line and human small cell lung cancer (SCLC) of the LTEP-P line were cultured and were divided into 3 groups respectively: control group, 15d-PGJ 2 group (15d-PGJ 2, a PPAR-γ activator, was added), and ciglitazone group (ciglitazone, am antidiabetic drug, was added). Twenty-four, forty-eight, and seventy-two hours later, nested RT-PCR was used to detect t the expression of PPAR-γ mRNA, Western blotting technique was used to detect the expression of PPAR-γ protein, MTT staining was used to observe the proliferation of cells induced by PPAR-γ agonists, TUNEL method was used to observe the apoptosis of cells affected by the ligands of PPAR-γ, the expressions of bax, and bcl-2 mRN and proteins were examined by in situ hybridization and immunohistochemistry, and the expression of caspase-3 was detected by immunohistochemistry. Results PPAR-γ was expressed in the two lung cancer cell lines. The cell proliferation was inhibited by 15d-PGJ 2 and ciglitazone, especially the former, in dose-dependent and time-dependent manners. The apoptosis rates were (1.9±0.5)%, (9.8±1.5)%, and (5.6±1.1)% respectively in the control, 15d-PGJ 2, and ciglitazone groups with a significant difference between ant 2 groups (all P <0.05). The expression rate of bax were (9,2±1.5)%, (63±10)%, and (31±6)% respectively in the control, 15d-PGJ 2, and ciglitazone groups with a very significant difference between ant 2 groups (all P <0.01). he expression rate of bcl-2 were (18±3)%, (36±9)%, and (33±7)% respectively in the control, 15d-PGJ 2, and ciglitazone groups with a very significant difference between the control group and any of the agonist-treated groups (all P <0.01) and without significant difference between the two treated groups. The expression rates of caspase-3 were (6.5±1.0)%, (65±11)%

关 键 词：活化 过氧化物酶体增生物激活受体-Γ 诱导 肺癌细胞 细胞凋亡 

分 类 号：R734.2[医药卫生—肿瘤]