Cell cycle perturbations in cisplatin-sensitive and resistant human ovarian carcinoma cells following treatment with cisplatin and low dose rate irradiation

Cancer Chemotherapy and Pharmacology
D E WilkinsG P Raaphorst

Abstract

To investigate cell cycle pertubations in plateau-phase human ovarian carcinoma cells following treatment with cisplatin, low dose-rate irradiation (LDRI), or combined cisplatin and LDRI, in order to understand cell cycle mechanisms by which these two treatment modalities interact. Human ovarian carcinoma cells sensitive (A2780) and resistant (2780CP) to cisplatin were grown to plateau phase and given protracted cisplatin treatments (A2780 0.7 and 2 microg/ml; 2780CP 5 and 15 microg/ml) and/or LDRI (0.41 cGy/min). Cell cycle distribution following treatment was determined by two-parameter flow cytometry, based on bromodeoxyuridine (BrdU) uptake and DNA content using propidium iodide staining. The cisplatin-sensitive A2780 cells exposed to cisplatin alone for up to 28 h showed depletion of the G1 fraction and accumulation in S-phase, although the percentage of S-phase cells actively incorporating BrdU dropped to almost zero. The cisplatin-resistant 2780CP cells exposed to cisplatin alone showed a G1 arrest when exposed to 15 microg/ml, but not when exposed to 5 microg/ml. LDRI alone caused little cell cycle redistribution different from controls in either cell line. When LDRI was combined with cisplatin, no significant cell cycl...Continue Reading

Citations

May 12, 2005·Molecular Cancer Research : MCR·Heather J BoeckmanJohn J Turchi
Mar 6, 2007·Critical Reviews in Oncology/hematology·David J Stewart
Aug 17, 2017·Dalton Transactions : an International Journal of Inorganic Chemistry·Yue ZhengZong-Wan Mao
Jan 18, 2019·PloS One·Alena MrkvicovaMartina Rezacova

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