title: Impact of PLK-1 silencing on endothelial cells and cancer cells of diverse histological origin.
abstract: The main goal of this work was to assess in vitro the potential of Polo-like kinase gene (PLK-1) as a molecular target within the tumor microenvironment, namely in both cancer cells of tumors of different histological origin and endothelial cells from angiogenic blood vessels, upon silencing with anti-PLK-1 siRNA. In addition, the effect of Plk-1 downregulation on the cancer cells chemosensitization to paclitaxel was further assessed. Downregulation of Plk-1 reduced cancer cells viability from 40 to 85% and up to 59% in endothelial cells. Regarding the latter, it compromised their ability to form new tube-like structures, decreasing the formation of network projections up to 46%. This suggested for the first time, PLK-1 as a valuable angiogenic molecular target. In combination with paclitaxel, anti-PLK-1 siRNA chemosensitized non-small cell lung cancer (NSCLC) and prostate carcinoma cell lines, leading up to a 2-fold increase in the drug cytotoxic effect. Moreover, the sequential incubation of anti-PLK-1 siRNA and paclitaxel led to a decrease in the IC50 of the latter up to 2.7- and 4.1-fold, in A-549 and PC-3 cells, respectively. The combination of anti-PLK-1 siRNA with paclitaxel led to cell cycle arrest, increasing the number of cells at the G2/M and S phases to 1.5 and 1.3-fold in PC-3 cells, and to 1.6 and 1.4-fold in A-549 cells, respectively. Overall, it has been demonstrated that PLK-1 silencing with siRNA can impact multiple cellular players of tumor aggressiveness, thus enabling the opportunity to interfere with different hallmarks of cancer, in tumors with diverse histological origin.
authors.affiliation: Center for Neurosciences and Cell Biology, University of Coimbra, Largo Marques de Pombal, 3004-517 Coimbra, Portugal.
authors.forename: Carla P
authors.initials: CP
authors.lastname: Gomes
authors.forename: Lígia C
authors.initials: LC
authors.lastname: Gomes-da-Silva
authors.forename: José S
authors.initials: JS
authors.lastname: Ramalho
authors.forename: Maria C P
authors.initials: MC
authors.lastname: de Lima
authors.forename: Sérgio
authors.initials: S
authors.lastname: Simões
authors.forename: João N
authors.initials: JN
authors.lastname: Moreira
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015536:Down-Regulation; D042783:Endothelial Cells / Q000201:enzymology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D012016:Reference Values; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology*; D059016:Tumor Microenvironment; D000097869:Polo-Like Kinase 1
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D017239:Paclitaxel; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D000097869:Polo-Like Kinase 1