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Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer

(2018) ONCOTARGET. 9(47). p.28731-28744
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Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells without causing damage to normal cells. However, some tumors are resistant to TRAIL monotherapy and clinical studies assessing targeted agents towards the TRAIL receptor have failed to show robust therapeutic activity. Evidence has shown that standard anti-mitotic drugs can induce synergistic apoptosis upon combination with TRAIL via cell cycle arrest. Polo like kinase-1 (PLK1) plays a critical role in different stages of cell cycle progression and mitosis. A number of investigations have demonstrated that PLK1 inhibition causes cell cycle arrest and mitotic catastrophe in non-small cell lung cancer (NSCLC), and we thus postulated that PLK1 inhibition could enhance TRAIL-induced apoptosis. We demonstrate that the combination of a TRAIL receptor agonist and a PLK1 inhibitor synergistically reduces cell viability, and strongly increases apoptosis in NSCLC cellular models. Consistent with our in vitro observations, this drug combination also significantly reduces tumor growth in vivo. Our data additionally reveal that G2/M cell cycle arrest and downregulation of Mcl-1 and signal transducer and activator of transcription 3 (STAT3) activity following PLK1 inhibition may contribute to the sensitization of TRAIL-induced apoptosis in NSCLC. Together, these data support the further exploration of combined TRAIL and PLK1 inhibition in the treatment of NSCLC.

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Chicago
Noor, Alfiah, Ijeoma Adaku Umelo, Peter Kronenberger, Philipe Giron, Elly De Vlieghere, Olivier De Wever, Erik Teugels, and Jacques De Grève. 2018. “Targeting Polo-like Kinase 1 and TRAIL Enhances Apoptosis in Non-small Cell Lung Cancer.” Oncotarget 9 (47): 28731–28744.
APA
Noor, A., Umelo, I. A., Kronenberger, P., Giron, P., De Vlieghere, E., De Wever, O., Teugels, E., et al. (2018). Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer. ONCOTARGET, 9(47), 28731–28744.
Vancouver
1.
Noor A, Umelo IA, Kronenberger P, Giron P, De Vlieghere E, De Wever O, et al. Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer. ONCOTARGET. 2018;9(47):28731–44.
MLA
Noor, Alfiah, Ijeoma Adaku Umelo, Peter Kronenberger, et al. “Targeting Polo-like Kinase 1 and TRAIL Enhances Apoptosis in Non-small Cell Lung Cancer.” ONCOTARGET 9.47 (2018): 28731–28744. Print.
@article{8579916,
  abstract     = {Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in cancer cells without causing damage to normal cells. However, some tumors are resistant to TRAIL monotherapy and clinical studies assessing targeted agents towards the TRAIL receptor have failed to show robust therapeutic activity. Evidence has shown that standard anti-mitotic drugs can induce synergistic apoptosis upon combination with TRAIL via cell cycle arrest. Polo like kinase-1 (PLK1) plays a critical role in different stages of cell cycle progression and mitosis. A number of investigations have demonstrated that PLK1 inhibition causes cell cycle arrest and mitotic catastrophe in non-small cell lung cancer (NSCLC), and we thus postulated that PLK1 inhibition could enhance TRAIL-induced apoptosis. We demonstrate that the combination of a TRAIL receptor agonist and a PLK1 inhibitor synergistically reduces cell viability, and strongly increases apoptosis in NSCLC cellular models. Consistent with our in vitro observations, this drug combination also significantly reduces tumor growth in vivo. Our data additionally reveal that G2/M cell cycle arrest and downregulation of Mcl-1 and signal transducer and activator of transcription 3 (STAT3) activity following PLK1 inhibition may contribute to the sensitization of TRAIL-induced apoptosis in NSCLC. Together, these data support the further exploration of combined TRAIL and PLK1 inhibition in the treatment of NSCLC.},
  author       = {Noor, Alfiah and Umelo, Ijeoma Adaku and Kronenberger, Peter and Giron, Philipe and De Vlieghere, Elly and De Wever, Olivier and Teugels, Erik  and De Gr{\`e}ve, Jacques},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  language     = {eng},
  number       = {47},
  pages        = {28731--28744},
  title        = {Targeting Polo-like kinase 1 and TRAIL enhances apoptosis in non-small cell lung cancer},
  url          = {http://dx.doi.org/10.18632/oncotarget.25618},
  volume       = {9},
  year         = {2018},
}

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