Impact of PLK-1 silencing on endothelial cells and cancer cells of diverse histological origin

Carla P. Gomes, Lígia C. Gomes-da-Silva, José S. Ramalho, Maria C.P. de Lima, Sérgio Simões, João N. Moreira

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)189-201
Number of pages13
JournalCurrent Gene Therapy
Volume13
Issue number3
DOIs
Publication statusPublished - 11 Jun 2013

Keywords

  • Angiogenesis
  • Cancer
  • Drug combination
  • Paclitaxel
  • Plk-1
  • Sirna
  • Tumor microenvironment

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