title: Formononetin inhibits human bladder cancer cell proliferation and invasiveness via regulation of miR-21 and PTEN.
abstract: The isoflavone formononetin is the main active component of Astragalus membranaceus and possesses anti-tumorigenic properties. However, the role of formononetin in human bladder cancer (BCa) has not been fully elucidated. The aim of the present study was to investigate the anti-tumor effects of formononetin on BCa cells and its potential molecular mechanism. T24 cells were treated with different concentrations of formononetin, and then the cell proliferation was assessed by MTT assay, cell apoptosis by Hoechst 33258 stain assay, cell invasiveness by transwell invasion assay, microRNA-21 (miR-21) expression by real-time PCR and the protein level of phosphatase and tensin homolog (PTEN) and phosphorylated homolog of Akt (p-Akt) by western blotting. The results showed that formononetin significantly inhibited the proliferation of T24 cells in a time- and dose-dependent manner. T24 cells treated with formononetin displayed obvious morphological changes of apoptosis and lower invasiveness. In addition, miR-21 expression was significantly decreased in formononetin-treated T24 cells, followed by increase of PTEN, and down-regulation of p-Akt. Collectively, these results suggest that formononetin exerts an anti-carcinogenic effect on BCa in vitro, which might be due to miR-21-mediated regulation of the PTEN/Akt pathway.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu 610083, China.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin 541004, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Second Affiliated Hospital of Guangxi Medical University, Nanning 530023, China.
authors.forename: Zhengzhao
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. yeyu9698@163.com.
authors.forename: Haibiao
authors.initials: H
authors.lastname: Yan
authors.affiliation: Department of Radiation Oncology of Clinical Cancer Center, the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China. janusy@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Qin
authors.affiliation: Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. yeyu9698@163.com.
authors.forename: Tianyu
authors.identifier: http://orcid.org/0000-0002-7025-436X
authors.initials: T
authors.lastname: Li
mesh_terms: D027883:Astragalus Plant / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D004365:Drugs, Chinese Herbal; D007529:Isoflavones; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C007768:formononetin; D051059:PTEN Phosphohydrolase