title: Platinum-zoledronate complex blocks gastric cancer cell proliferation by inducing cell cycle arrest and apoptosis.
abstract: A series of novel dinuclear platinum complexes based on the bisphosphonate ligands have been synthesized and characterized in our recent study. For the purpose of discovering the pharmacology and action mechanisms of this kind of compounds, the most potent compound [Pt(en)]2ZL was selected for systematic investigation. In the present study, the inhibition effect on the human gastric cancer cell lines SGC7901 and action mechanism of [Pt(en)]2ZL were investigated. The traditional 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and colony formation assay were carried out to study the effect of [Pt(en)]2ZL on the cell viability and proliferation capacity, respectively. The senescence-associated β-galactosidase staining and immunofluorescence staining were also performed to assess the cell senescence and microtubule polymerization. Fluorescence staining and flow cytometry (FCM) were used to monitor the cell cycle distribution and apoptosis, and Western blot analysis was applied to examine the expression of several apoptosis-related proteins. The results demonstrated that [Pt(en)]2ZL exhibited remarkable cytotoxicity and anti-proliferative effects on the SGC7901 cells in a dose- and time-dependent manner, and it also induced cell senescence and abnormal microtubule assembly. The cell apoptosis and cell cycle arrest induced by [Pt(en)]2ZL were also observed with the fluorescence staining and FCM. The expressions of cell cycle regulators (p53, p21, cyclin D1, cyclin E, and cyclin-dependent kinase (CDK)2) and apoptosis-related proteins (Bcl-2, Bax, caspase-3, poly ADP ribose polymerase (PARP), and survivin) were regulated by the treatment of [Pt(en)]2ZL, resulting in the cell cycle arrest and apoptosis. Therefore, [Pt(en)]2ZL exerted anti-tumor effect on the gastric cancer via inducing cell cycle arrest at G1/S phase and apoptosis.
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Gaochao
authors.initials: G
authors.lastname: Lv
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China.
authors.forename: Huixin
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. xieminhao@jsinm.org.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China. xieminhao@jsinm.org.
authors.forename: Minhao
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Radiation Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China. linjianguo@jsinm.org.|Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 214063, China. linjianguo@jsinm.org.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D017671:Platinum Compounds / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D017671:Platinum Compounds; D000077211:Zoledronic Acid
keywords: Apoptosis; Cell cycle arrest; Human gastric cancer cell line SGC7901; Platinum-zoledronate complex