Fengyun Wang1, Yang Liu2, Zhenyu Bi3. 1. a Department of Ophthalmology , The First Affiliated Hospital, Henan University of Science and Technology , Luoyang , Henan , PR China. 2. b Department of Stomatology, Nanfang Hospital, Southern Medical University , Guangzhou , Guangdong Province , PR China. 3. c Department of Anatomy, Key Laboratory of Medical Biomechanics of Guangdong Province , Southern Medical University , Guangzhou , Guangdong Province , PR China.
Abstract
OBJECTIVES: We aimed to study the antitumor effects of the PPARγ agonist pioglitazone on human retinoblastoma. METHODS: The effects of pioglitazone on cell proliferation and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hoechst 33258 staining assay. The apoptosis related protein levels were detected by western blot. Inflammationary factors analysis was evaluated by western blot and ELISA. The effect of pioglitazone on nuclear factor-kappa B (NF-κB)-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay. Then human retinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice and the animals were treated with pioglitazone to verify its antitumor effect in vivo. RESULTS: Our data revealed that pioglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that pioglitazone could affect the apoptosis and inflammation related signal via modulating the activity of NF-κB signal. Also we found that pioglitazone could markedly reduce the growth of Y79 cells transplanted into the mice without causing significant side effects. CONCLUSIONS: Our results suggested that pioglitazone demonstrated antitumor activity against the human retinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and modulating NF-κB pathway, and thus delayed tumor growth in vivo.
OBJECTIVES: We aimed to study the antitumor effects of the PPARγ agonist pioglitazone on humanretinoblastoma. METHODS: The effects of pioglitazone on cell proliferation and apoptosis of the humanretinoblastoma Y79 cells were investigated by MTT assay and Hoechst 33258 staining assay. The apoptosis related protein levels were detected by western blot. Inflammationary factors analysis was evaluated by western blot and ELISA. The effect of pioglitazone on nuclear factor-kappa B (NF-κB)-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay. Then humanretinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice and the animals were treated with pioglitazone to verify its antitumor effect in vivo. RESULTS: Our data revealed that pioglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that pioglitazone could affect the apoptosis and inflammation related signal via modulating the activity of NF-κB signal. Also we found that pioglitazone could markedly reduce the growth of Y79 cells transplanted into the mice without causing significant side effects. CONCLUSIONS: Our results suggested that pioglitazone demonstrated antitumor activity against the humanretinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and modulating NF-κB pathway, and thus delayed tumor growth in vivo.
Authors: Marcelle Silva-Abreu; Lupe Carolina Espinoza; María José Rodríguez-Lagunas; María-José Fábrega; Marta Espina; María Luisa García; Ana Cristina Calpena Journal: Int J Mol Sci Date: 2017-11-28 Impact factor: 5.923