Zhang Min, Zou Ping, Bai Ming, Tao Xiao-nan, Jin Yang, Guo Rong
Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Zhonghua Yi Xue Za Zhi. 2003 Jul 10;83(13):1169-72.
To explore the effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the growth of human lung cancer cell lines and its possible mechanism.
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-gamma 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-gamma mRNA, Western blotting technique was used to detect the expression of PPAR-gamma protein, MTT staining was used to observe the proliferation of cells induced by PPAR-gamma agonists, TUNEL method was used to observe the apoptosis of cells affected by the ligands of PPAR-gamma, 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.
PPAR-gamma 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)%, and (40 +/- 7)% respectively in the control, 15d-PGJ(2), and ciglitazone groups with a significant difference between any 2 group (all P < 0.01). The caspase-3 level was positively correlated with the level of apoptosis.
Activated by ligands, PPAR-gamma remarkably inhibits the growth of human lung cancer cells through inducing apoptosis. Caspase-3 and bax/bcl-2 play a role in this process, PPAR-gamma is so important in the pathogenesis and/or progression of lung cancer that it may be a novel therapeutical target against lung cancer.
探讨过氧化物酶体增殖物激活受体γ（PPAR-γ）对人肺癌细胞系生长的影响及其可能机制。
培养人A549系非小细胞肺癌（NSCLC）细胞和人LTEP-P系小细胞肺癌（SCLC）细胞，并分别分为3组：对照组、15d-PGJ(2)组（加入PPAR-γ激活剂15d-PGJ(2)）和吡格列酮组（加入抗糖尿病药物吡格列酮）。24、48和72小时后，采用巢式RT-PCR检测PPAR-γ mRNA的表达，采用蛋白质印迹技术检测PPAR-γ蛋白的表达，采用MTT染色观察PPAR-γ激动剂诱导的细胞增殖，采用TUNEL法观察PPAR-γ配体影响的细胞凋亡，通过原位杂交和免疫组织化学检测bax和bcl-2 mRNA及蛋白的表达，通过免疫组织化学检测caspase-3的表达。
PPAR-γ在两种肺癌细胞系中均有表达。15d-PGJ(2)和吡格列酮抑制细胞增殖，尤其是前者，呈剂量和时间依赖性。对照组、15d-PGJ(2)组和吡格列酮组的凋亡率分别为(1.9±0.5)%、(9.8±1.5)%和(5.6±1.1)%，任意两组之间差异均有统计学意义（均P<0.05）。对照组、15d-PGJ(2)组和吡格列酮组的bax表达率分别为(9.2±1.5)%、(63±10)%和(31±6)%，任意两组之间差异均有极显著统计学意义（均P<0.01）。对照组、15d-PGJ(2)组和吡格列酮组的bcl-2表达率分别为(18±3)%、(36±9)%和(33±7)%，对照组与任意一个激动剂处理组之间差异均有极显著统计学意义（均P<0.01），两个处理组之间无显著差异。对照组、15d-PGJ(2)组和吡格列酮组的caspase-3表达率分别为(6.5±1.0)%、(65±11)%和(40±7)%，任意两组之间差异均有统计学意义（均P<0.01）。caspase-3水平与凋亡水平呈正相关。
PPAR-γ被配体激活后，通过诱导凋亡显著抑制人肺癌细胞的生长。Caspase-3和bax/bcl-2在此过程中发挥作用，PPAR-γ在肺癌的发病机制和/或进展中非常重要，可能是一种新型的肺癌治疗靶点。
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