Jenny Ling-Yu Chen1,2,3, Jo-Pai Chen3,4, Yu-Sen Huang5,6,7, Yuan-Chun Tsai1, Ming-Hsien Tsai1, Fu-Shan Jaw1, Jason Chia-Hsien Cheng3,8, Sung-Hsin Kuo3,8, Ming-Jium Shieh1,3. 1. Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan. 2. Department of Radiation Oncology, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan. 3. Department of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan. 4. Department of Oncology, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. 5. Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan. yusen0814@gmail.com. 6. Department of Medical Imaging, National Taiwan University Hospital, No.7, Chung-Shan South Road, 100, Taipei, Taiwan. yusen0814@gmail.com. 7. Department of Medical Imaging, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan. yusen0814@gmail.com. 8. Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan.
Abstract
PURPOSE: This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. METHODS AND MATERIALS: Human esophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. RESULTS: Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. CONCLUSIONS: The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone.
PURPOSE: This study examined the efficacy of polo-like kinase 1 (PLK1) inhibition on radiosensitivity in vitro and in vivo by a pharmacologic approach using the highly potent PLK1 inhibitor volasertib. METHODS AND MATERIALS: Humanesophageal squamous cell carcinoma (ESCC) cell lines KYSE 70 and KYSE 150 were used to evaluate the synergistic effect of volasertib and irradiation in vitro using cell viability assay, colony formation assay, cell cycle phase analysis, and western blot, and in vivo using ectopic tumor models. RESULTS:Volasertib decreased ESCC cell proliferation in a dose- and time-dependent manner. Combination of volasertib and radiation caused G2/M cell cycle arrest, increased cyclin B levels, and induced apoptosis. Volasertib significantly enhanced radiation-induced death in ESCC cells by a mechanism involving the enhancement of histone H3 phosphorylation and significant cell cycle interruption. The combination of volasertib plus irradiation delayed the growth of ESCC tumor xenografts markedly compared with either treatment modality alone. CONCLUSIONS: The in vitro results suggested that targeting PLK1 might be a viable approach to improve the effects of radiation in ESCC. In vivo studies showed that PLK1 inhibition with volasertib during irradiation significantly improved local tumor control when compared to irradiation or drug treatment alone.
Authors: Kate Gerster; Wei Shi; Benjamin Ng; Shijun Yue; Emma Ito; John Waldron; Ralph Gilbert; Fei-Fei Liu Journal: Int J Radiat Oncol Biol Phys Date: 2010-05-01 Impact factor: 7.038
Authors: Jolien Van den Bossche; Andreas Domen; Marc Peeters; Christophe Deben; Ines De Pauw; Julie Jacobs; Sven De Bruycker; Pol Specenier; Patrick Pauwels; Jan Baptist Vermorken; Filip Lardon; An Wouters Journal: Cancers (Basel) Date: 2019-11-28 Impact factor: 6.639