title: Anti-tumor effects of bemiparin in HepG2 and MIA PaCa-2 cells.
abstract: Recent researches have demonstrated improved survival in oncologic patients treated with low molecular weight heparins (LMWHs) which are anticoagulant drugs. We evaluated "second generation" LMWH bemiparin and its in vitro anti-tumor effects on HepG2 hepatocellular carcinoma and MIA PaCa-2 cancer cells. The aim of the study is to investigate anti-cancer mechanism of bemiparin in HepG2 and Mia-Paca-2 cancer cells. Cytotoxic effects of bemiparin were determined by XTT assay. IC50 dose of bemiparin was found to be 200 IU/mL in the 48th hour in the MiaPaCa-2 cell line and 50 IU/mL in the 48th hour in the HepG2 cell line. CCND1 (cyclin D1), CDK4, CDK6, p21, p16, p53, caspase-3, caspase-9, caspase-8, Bcl-2, BID, DR4, DR5, FADD, TRADD, Bax, gene mRNA expressions were evaluated by Real-time PCR. Real-time PCR analysis showed that CCND1 expression was reduced in HepG2 dose the group cells when compared with the control group cells and p53, caspase-3, caspase p21, caspase-8 and expressions were increased in the dose group cells when compared with the control group cells. CCND1, CDK4 and CDK6 expressions were reduced in MIA PaCa-2 dose group cells when compared with the control group cells and p53 expression was increased in the dose group cells when compared with the control group cells. Other expressions of genes were found statistically insignificant both of cell lines. It was found that bemiparin in HepG2 and MIA PaCa-2 cells suppressed invasion, migration, and colony formation by using matrigel invasion chamber, and colony formation assay, respectively. In conclusion, it is thought that bemiparin indicates anti-tumor activity by affecting cell cycle arrest, apoptosis, invasion, migration, and colony formation on cancer cells.
authors.affiliation: Department of Cardiovascular Surgery, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
authors.forename: İhsan
authors.initials: İ
authors.lastname: Alur
authors.affiliation: Department of Medical Biology and Genetics, Pamukkale University, Faculty of Medicine, Denizli, Turkey. Electronic address: yavuzdodurga@gmail.com.
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Dodurga
authors.affiliation: Department of Medical Biology and Genetics, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
authors.forename: Mücahit
authors.initials: M
authors.lastname: Seçme
authors.affiliation: Department of Medical Biology and Genetics, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
authors.forename: Levent
authors.initials: L
authors.lastname: Elmas
authors.affiliation: Department of Medical Biology and Genetics, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
authors.forename: Gülseren
authors.initials: G
authors.lastname: Bağcı
authors.affiliation: Department of Cardiovascular Surgery, Pamukkale University, Faculty of Medicine, Denizli, Turkey.
authors.forename: İbrahim
authors.initials: İ
authors.lastname: Gökşin
authors.affiliation: Department of Medical Biology and Genetics, Ege University, Faculty of Medicine, İzmir, Turkey.
authors.forename: Çığır Biray
authors.initials: ÇB
authors.lastname: Avcı
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D018816:Genes, cdc / Q000187:drug effects; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D006495:Heparin, Low-Molecular-Weight; C411345:bemiparin
keywords: Bemiparin; HepG2; MIA PaCa-2