title: Downregulation of Kinesin spindle protein inhibits proliferation, induces apoptosis and increases chemosensitivity in hepatocellular carcinoma cells.
abstract: Kinesin spindle protein (KSP) plays a critical role in mitosis. Inhibition of KSP function leads to cell cycle arrest at mitosis and ultimately to cell death. The aim of this study was to suppress KSP expression by specific small-interfering RNA (siRNA) in Hep3B cells and evaluate its anti-tumor activity.
  
  
  
  Three siRNA targeting KSP (KSP-siRNA #1-3) and one mismatched-siRNA (Cont-siRNA) were transfected into cells. Subsequently, KSP mRNA and protein levels, cell proliferation, and apoptosis were examined in both Hep3B cells and THLE-3 cells. In addition, the chemosensitivity of KSP-siRNA-treated Hep3B cells with doxorubicin was also investigated using cell proliferation and clonogenic survival assays.
  
  
  
  The expression of endogenous KSP at both mRNA and protein levels in Hep3B cells was higher than in THLE-3 cells. In Hep3B cells, KSP-siRNA #2 showed a further downregulation of KSP as compared to KSP-siRNA #1 or KSP-siRNA #3. It also exhibited greater suppression of cell proliferation and induction of apoptosis than KSP-siRNA #1 or KSP-siRNA #3; this could be explained by the significant downregulation of cyclin D1, Bcl-2, and survivin. In contrast, KSP-siRNAs had no or lower effects on KSP expression, cell proliferation and apoptosis in THLE-3 cells. We also noticed that KSP-siRNA transfection could increase chemosensitivity to doxorubicin in Hep3B cells, even at low doses compared to control.
  
  
  
  Reducing the expression level of KSP, combined with drug treatment, yields promising results for eradicating hepatocellular carcinoma (HCC) cells in vitro. This study opens a new direction for liver cancer treatment.
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Chinh Chung
authors.initials: CC
authors.lastname: Doan
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Ngoc Trung
authors.initials: NT
authors.lastname: Doan
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Quang Huy
authors.initials: QH
authors.lastname: Nguyen
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Minh Hoa
authors.initials: MH
authors.lastname: Nguyen
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.
authors.forename: Minh Si
authors.initials: MS
authors.lastname: Do
authors.affiliation: Faculty of Biology, University of Science, Vietnam National University, 227 Nguyen Van Cu Street, Ward 4, District 5, Ho Chi Minh City, Vietnam.|Dept. of  Immunology, Vietnam Military Medical University, 
  160 Phung Hung Street, Ha Dong District, Ha Noi City, Vietnam.
authors.forename: Van Dong
authors.initials: VD
authors.lastname: Le
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis; D016547:Kinesins / Q000096:biosynthesis / Q000235:genetics*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008938:Mitosis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D000077022:Survivin
chemical_list: D000903:Antibiotics, Antineoplastic; C107489:BIRC5 protein, human; C530104:CCND1 protein, human; D051034:Inhibitor of Apoptosis Proteins; C470243:KIF11 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D000077022:Survivin; D019938:Cyclin D1; D004317:Doxorubicin; D016547:Kinesins
keywords: Apoptosis; Chemosensitivity; Doxorubicin; Hepatocellular carcinoma cells; Kinesin spindle protein