Title: Mechanisms of Cell Sensitization to Alpha-Radioimmunotherapy by Doxorubicin or Paclitaxel in MultipleMyeloma Cell Lines
Authors: SUPIOT S.GOUARD S.CHARRIER J.APOSTOLIDIS CHRISTOSCHATAL J.-F.BARBET J.DAVODEAU F.CHEREL M.
Citation: CLINICAL CANCER RESEARCH vol. 11 no. 19 p. 7047s-7052s
Publisher: AMER ASSOC CANCER RESEARCH
Publication Year: 2005
JRC N°: JRC30884
URI: http://publications.jrc.ec.europa.eu/repository/handle/JRC30884
Type: Articles in Journals
Abstract: Purpose:The purpose of this studywas to analyze differentmechanisms (cell cycle synchronization, DNA damage, and apoptosis) that might underlie potential synergy between chemotherapy (paclitaxel or doxorubicin) and radioimmunotherapy with a radionuclides. Experimental Design:Threemultiplemyeloma cell lines (LP1, RMI 8226, and U266)were treatedwith 213Bi-radiolabeledB-B4, amonoclonal antibody that recognizes syndecan-1 (CD138) 24 hours after paclitaxel (1nmol/L) or doxorubicin (10 nmol/L) treatment.Cell survivalwas assessed using a clonogenic survival assay. Cell cycle modifications were assessed by propidium iodide staining and DNA strand breaks by the comet assay. Level of apoptosis was determined by Apo 2.7 staining. Results: Radiation enhancement ratio showed that paclitaxel and doxorubicin were synergistic with a radioimmunotherapy.After a 24-hour incubation, paclitaxel and doxorubicinarrested all cell lines in the G2-M phase of the cell cycle. Doxorubicin combined with a radioimmunotherapy increased tail DNA in the RPMI 8226 cell line but not the LP1or U266 cell lines compared with doxorubicin alone or a radioimmunotherapy alone. Neither doxorubicin nor paclitaxel combined with a radioimmunotherapy increased the level of apoptosis induced by either drug alone or a radioimmunotherapy alone. Conclusion: Both cell cycle arrest in the G2-M phase and an increase in DNA double-strand breaks could lead to radiosensitization of cells by doxorubicin or paclitaxel, but apoptosis would not be involved in radiosensitizationmechanisms.
JRC Institute:Institute for Transuranium Elements

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