Rituximab sensitizes a Burkitt lymphoma cell line to cell killing by X-irradiation.
Clinical trials with rituximab in combination with chemotherapeutic regimens have shown promising results. Data on the effects of rituximab treatment in combination with irradiation are, however, limited and inconsistent. This study aims to investigate the effects of rituximab (R) on cell death induced by X-irradiation in Raji lymphoma cells and to evaluate its mechanisms. We found the cell growth inhibition by irradiation was enhanced by additional rituximab exposure both in cells precultured with rituximab followed by irradiation (R + irradiation) or in cells treated in the reverse sequence (irradiation + R). R + irradiation combination treatment induced more apoptotic cells than irradiation and irradiation + R treatment as early as 12 h after treatment. At 24 h, both combination treatments, R + irradiation and irradiation + R, showed apoptotic cells, which were significantly different from irradiation alone. G2/M cell cycle arrest was observed after irradiation alone and the combination treatment. The combination treatment revealed an elevation in reactive oxygen species (ROS) generation in a radiation dose-dependent manner. In addition, rituximab enhanced the cell growth inhibition and apoptotic cell death induced by the oxidative agent, H(2)O(2). We propose that rituximab mediates a significant in vitro radiosensitizing effect and induces cell cycle changes and apoptosis in Raji cells. ROS probably play an important role in these events.
Fengling
Min
M
School of Radiation Medicine and Public Health, Soochow University, 215006, Suzhou, China.
Fenju
Liu
L
Wanxin
Wen
W
Lijia
Zhai
Z
Jiandong
Tong
T
Zu
Wang
W
Xin
Yuan
Y
Qingxiang
Gao
G
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000503:physiopathology / Q000532:radiotherapy*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D016923:Cell Death / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000069283:Rituximab; D013050:Spectrometry, Fluorescence; D014965:X-Rays
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D000069283:Rituximab; D006861:Hydrogen Peroxide