Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells
Activation of the PPAR pathway induces apoptosis and COX-2 inhibition in HT-29 human colon cancer cells
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DOI：
10.1093/carcin/22.9.1379
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发表时间：
2001-09-01
期刊：
影响因子：
4.7
通讯作者：
Frucht, H
中科院分区：
文献类型：
--
作者：
Yang, WL;Frucht, H
过氧化物酶体增殖物激活受体（PPARgamma）的γ亚型是一种调节脂肪细胞分化的核受体。近年来研究发现其在人结肠黏膜和结肠癌中表达，但其在结肠癌发生发展中的作用尚不清楚。我们证明，激活的PPAR γ环格列酮（CIG），一种选择性的PPAR γ配体，诱导HT-29人结肠癌细胞凋亡。cig治疗还下调环氧化酶-2（考克斯-2）蛋白的表达。与单独使用cig或9-cis-RA处理的细胞相比，同时暴露于cig和9-cis-RA（维甲酸X受体的配体）导致细胞凋亡效应增加和考克斯-2表达抑制增加。由于考克斯-2在人结肠癌中过表达，并与增强侵袭性和肿瘤发生性有关，因此PPAR γ活化降低考克斯-2表达和诱导细胞凋亡的能力表明，PPAR γ途径可被视为结肠癌的治疗靶点。
The gamma isoform of the peroxisome proliferator-activated receptor (PPAR gamma) is a nuclear receptor that regulates adipocyte differentiation. Recently it has been shown to be expressed in human colonic mucosa and cancer, but its role in colon carcinogenesis and progression is still unclear. We demonstrate that activation of PPAR gamma by ciglitazone (cig), a selective PPAR gamma ligand, induces HT-29 human colon cancer cells to undergo apoptosis. Treatment with cig also down-regulates expression of cyclooxygenase-2 (COX-2) protein. Simultaneous exposure of cells to cig and 9-cis-retinoic acid (9-cis-RA), a ligand for retinoid X receptor, results in an increased apoptotic effect and increased inhibition of COX-2 expression, compared with cells treated with either cig or 9-cis-RA alone. As COX-2 is overexpressed in human colon cancer and has been implicated in augmenting invasiveness and tumorigenecity, the ability of PPAR gamma activation to decrease COX-2 expression and induce apoptosis suggests that the PPAR gamma pathway may be considered as a therapeutic target for colon cancer.