title: Lobaplatin induces apoptosis and arrests cell cycle progression in human cholangiocarcinoma cell line RBE.
abstract: The aim of this study was to determine the anticancer effects of lobaplatin in cholangiocarcinoma (CCA) RBE cells. We also explored the mechanism of action of lobaplatin by analyzing its influence on apoptosis and cell cycle. Our findings have shown that lobaplatin inhibits cell proliferations in human CCA cells with an IC50 value of approximately 5.26±0.63 μg/mL. Flowcytometry assay confirmed that lobaplatin affected CCA cell survival by blocking cell cycle progression and inducing apoptosis. Lobaplatin treatment reduced Cyclin D1, CDK4, and CDK6 expression, which led to the blocking of G0/G1 transition. In addition, lobaplatin increased p53, Bax expression, caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage, and reduced Bcl-2 expression, which contributed to the apoptosis of CCA cells. Lobaplatin showed a good anti-tumour activity in in vitro models of human CCA cells. These results indicate that Lobaplatin, as the third-generation platinum antineoplastic agent, could be an effective chemotherapeutic agent in human CCA treatment through induction apoptosis and cell cycle arrest.
authors.affiliation: Department of Hepatobiliary Surgery, Beijing 302 Hospital, Beijing, China.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Wang
authors.forename: Xuelian
authors.initials: X
authors.lastname: Tang
authors.forename: Yilu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruizhao
authors.initials: R
authors.lastname: Qi
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.forename: Keming
authors.initials: K
authors.lastname: Zhang
authors.forename: Zhenwen
authors.initials: Z
authors.lastname: Liu
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D003503:Cyclobutanes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C530104:CCND1 protein, human; D003503:Cyclobutanes; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D011065:Poly(ADP-ribose) Polymerases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D053148:Caspase 3; C066228:lobaplatin