Abstract
Objective
To investigate the effect of activation of peroxisome proliferator-activated receptor gamma (PPARγ) on cell cycle arrest of gastric carcinoma cell line MGC803.
Methods
The inhibitory of pioglitazone (PGZ) on proliferation of MGC803 cells was analyzed by MTT assay. Cell cycle was detected by flow cytometry (FCM). The expressions of PPARγ, cyclin D1 and cell cycle protein-dependent kinase CDK4 in MGC803 cells were detected by reverse transcriptase-polymerase chain reaction (RT-PCR).
Results
Treatment with 0.1–10 μmol/L PGZ for 96 h significantly inhibited cell proliferation. The proportion of MGC803 cells at G1 phase was significantly increased when treated with 10 μmol/L PGZ for 48, 72 and 96 h, and showed an apparent G1 phase arrest. The expression of PPARγ was at a low level in MGC803 cells and significantly up-regulated when treated with 10 μmol/L PGZ for 48 h (P < 0.01). The expression of CDK4 in MGC803 cells was remarkably down-regulated when treated with 10 μmol/L PGZ for 48 h and the expression of cyclin D1 was slightly down-regulated (P < 0.01).
Conclusion
Activation of PPARγ significantly induced G1 phase arrest, which was associated with down-regulation of the expressions of CDK4 and cyclin D1.
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References
Rosen ED, Spiegelman BM. PPARgamma: a nuclear regulator of metabolism, differentiation, and cell growth. J Biol Chem, 2001, 276: 37731–37734.
Mueller E, Sarraf P, Tontonoz P, et al. Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell, 1998, 1: 465–470.
Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med, 1998, 4: 1046–1052.
Chang TH, Szabo E. Induction of differentiation and apoptosis by ligands of peroxisome proliferator-activated receptor gamma in non-small cell lung cancer. Cancer Res, 2000, 60: 1129–1138.
Elstner E, Müller C, Koshizuka K, et al. Ligands for peroxisome proliferator-activated receptorgamma and retinoic acid receptor inhibit growth and induce apoptosis of human breast cancer cells in vitro and in BNX mice. Proc Natl Acad Sci USA, 1998, 95: 8806–8811.
Kubota T, Koshizuka K, Williamson EA, et al. Ligand for peroxisome proliferator-activated receptor gamma (troglitazone) has potent antitumor effect against human prostate cancer both in vitro and in vivo. Cancer Res, 1998, 58: 3344–3352.
Tsubouchi Y, Sano H, Kawahito Y, et al. Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptorgamma agonists through induction of apoptosis. Biochem Biophys Res Commun, 2000, 270: 400–405.
Elnemr A, Ohta T, Iwata K, et al. PPARgamma ligand (thiazolidinedione) induces growth arrest and differentiation markers of human pancreatic cancer cells. Int J Oncol, 2000, 17: 1157–1164.
Yin F, Wakino S, Liu Z, et al. Troglitazone inhibits growth of MCF-7 breast carcinoma cells by targeting G1 cell cycle regulators. Biochem Biophys Res Commun, 2001, 286: 916–922.
Clay CE, Namen AM, Atsumi G, et al. Influence of J series prostaglandins on apoptosis and tumorigenesis of breast cancer cells. Carcinogenesis, 1999, 20: 1905–1911.
Rumi MA, Sato H, Ishihara S, et al. Peroxisome proliferator-activated receptor gamma ligand-induced growth inhibition of human hepatocellular carcinoma. Br J Cancer, 2001, 84: 1640–1647.
Watanabe Y, Watanabe T, Kitagawa M, et al. pRb phosphorylation is regulated differentially by cyclin-dependent kinase (Cdk) 2 and Cdk4 in retinoic acid induced neuronal differentiation of P19 cells. Brain Res, 1999, 842: 342–350.
Ko JK, Leunq WC, Ho WK, et al. Herbal diterpenoids induce growth arrest and apoptosis in colon cancer cells with increased expression of the nonsteroidal anti-inflammatory drug-activated gene. Eur J Pharmacol, 2007, 559: 1–13.
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Shi, J., Meng, A. & Liu, C. Effect of activation of PPARγ on cell cycle progression in human gastric carcinoma cells. Chin. -Ger. J. Clin. Oncol. 7, 534–537 (2008). https://doi.org/10.1007/s10330-008-0075-2
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DOI: https://doi.org/10.1007/s10330-008-0075-2