Yu Hong-Nu, Lee Young-Rae, Noh Eun-Mi, Lee Kyung-Sun, Kim Jong-Suk, Song Eun-Kyung, Han Myung-Kwan, Lee Yong-Chul, Kwon Kang-Beom, Lee Seung-Jin, Youn Hyun Jo, Jung Sung Hoo
Department of Biochemistry, Institute of Medical Science, Chonbuk National University Medical School, San 2-20 Geumam-dong, Deokjin-gu, Jeonbuk, Jeonju 560-182, South Korea.
Cell Biol Int. 2008 Aug;32(8):906-12. doi: 10.1016/j.cellbi.2008.04.011. Epub 2008 Apr 10.
Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands inhibit cell proliferation and induce apoptosis in cancer cells. Here we wished to determine whether the PPARgamma ligand induces apoptosis and cell cycle arrest of the MDA-MB-231 cell, an estrogen receptor alpha negative breast cancer cell line. The treatment of MDA-MB-231 cell with PPARgamma ligands was shown to induce inhibition of cell growth in a dose-dependent manner as determined by MTT assay. Cell cycle analysis showed a G1 arrest in MDA-MB-231 cells exposed to troglitazone. An apoptotic effect by troglitazone demonstrated that apoptotic cells elevated by 2.5-fold from the control level at 10 microM, to 3.1-fold at 50 microM and to 3.5-fold at 75 microM. Moreover, troglitazone treatment, applied in a dose-dependent manner, caused a marked decrease in pRb, cyclin D1, cyclin D2, cyclin D3, Cdk2, Cdk4 and Cdk6 expression as well as a significant increase in p21 and p27 expression. These results indicate that troglitazone causes growth inhibition, G1 arrest and apoptotic death of MDA-MB-231 cells.
过氧化物酶体增殖物激活受体γ（PPARγ）配体可抑制癌细胞的增殖并诱导其凋亡。在此，我们希望确定PPARγ配体是否能诱导雌激素受体α阴性乳腺癌细胞系MDA-MB-231细胞发生凋亡及细胞周期阻滞。通过MTT法测定发现，用PPARγ配体处理MDA-MB-231细胞可呈剂量依赖性地抑制细胞生长。细胞周期分析显示，暴露于曲格列酮的MDA-MB-231细胞出现G1期阻滞。曲格列酮的凋亡作用表明，凋亡细胞从对照水平在10微摩尔时升高2.5倍，在50微摩尔时升高3.1倍，在75微摩尔时升高3.5倍。此外，以剂量依赖性方式应用曲格列酮处理，可导致pRb、细胞周期蛋白D1、细胞周期蛋白D2、细胞周期蛋白D3、细胞周期蛋白依赖性激酶2（Cdk2）、细胞周期蛋白依赖性激酶4（Cdk4）和细胞周期蛋白依赖性激酶6（Cdk6）的表达显著降低，同时p21和p27的表达显著增加。这些结果表明，曲格列酮可导致MDA-MB-231细胞生长抑制、G1期阻滞及凋亡死亡。
