视黄醇 X 受体γ和过氧化物酶体增殖物激活受体γ配体联合抑制结肠癌的增殖和侵袭。

RXRgamma and PPARgamma ligands in combination to inhibit proliferation and invasiveness in colon cancer cells.

机构信息

Department of Experimental Evolutionary Biology, University of Bologna, Italy.

出版信息

Cancer Lett. 2010 Nov 1;297(1):65-74. doi: 10.1016/j.canlet.2010.04.026. Epub 2010 May 26.

DOI:10.1016/j.canlet.2010.04.026

PMID:20510503

Abstract

Nuclear retinoid X receptors (RXRs) and peroxisome proliferator-activated receptors (PPARs are potential candidates as drug target for cancer prevention and treatment. We investigated if the rexinoid 6-OH-11-O-hydroxyphenantrene (IIF) potentiates the antitumoral properties of PPARgamma ligands as ciglitazone and pioglitazone, on two colon cancer cell lines: HCA-7 and HCT-116. Drugs inhibited cell growth and induced apoptosis synergistically. The combination resulted in a decrease of cyclooxigenase-2, metalloproteinases-2 and -9 expression level and activity while PPARgamma, RXRgamma and tissue inhibitors of metalloproteinase-1 and -2 expression were increased. Finally, IIF potentiated PPAR transcriptional activity by enhancement of peroxisome proliferator response elements transactivation.

摘要

核视黄酸 X 受体（RXRs）和过氧化物酶体增殖物激活受体（PPARs）是作为癌症预防和治疗的药物靶点的潜在候选物。我们研究了 rexinoid 6-OH-11-O-羟基菲（IIF）是否增强了 PPARγ配体（如 ciglitazone 和 pioglitazone）的抗肿瘤特性，在两种结肠癌细胞系：HCA-7 和 HCT-116 上。药物协同抑制细胞生长并诱导细胞凋亡。该组合导致环氧合酶-2、金属蛋白酶-2 和 -9 的表达水平和活性降低，而 PPARγ、RXRγ 和组织金属蛋白酶抑制剂-1 和 -2 的表达增加。最后，IIF 通过增强过氧化物酶体增殖物反应元件的反式激活来增强 PPAR 转录活性。