Pretreatment with rituximab enhances radiosensitivity of non-Hodgkin's lymphoma cells.
The present study examines the effects of ionizing radiation in combination with rituximab (RTX), a chimeric human anti-CD20 monoclonal antibody, on proliferation, cell cycle distribution and apoptosis in B-lymphoma RL and Raji cells. Exposure to ionizing radiation (9 Gy) induced cell growth delay and apoptosis in RL cells, whereas Raji cells showed moderate radio-resistance. The simultaneous exposure of lymphoma cells to ionizing radiation and RTX (10 microg/mL) markedly enhanced apoptosis and cell growth delay in RL and Raji cells. Cooperative antiproliferative and apoptotic effects of RTX and radiation were achieved through the inhibition of c-myc and bcl-XL expression. Furthermore, RTX-modulated expression of cell cycle regulating proteins, such as p53, p21/WAF1, p27/KIP1, contributed to the development of radiation-induced cell killing and growth arrest. Each NHL cell line that underwent apoptosis induced by combination treatment revealed enhanced caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage as compared to only irradiated cells. These findings show that rituximab synergistically enhances radiation-induced apoptosis and cell growth delay through the expression of proteins involved in the programmed cell death and cell cycle regulation pathways.
Department of Radiotherapy-Radiooncology, Innsbruck Medical University, Austria. Ira.Skvortsova@uibk.ac.at
Ira
I
Skvortsova
Bela-Andre
BA
Popper
Sergej
S
Skvortsov
Maria
M
Saurer
Thomas
T
Auer
Robert
R
Moser
Hans
H
Kamleitner
Heinz
H
Zwierzina
Peter
P
Lukas
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008224:Lymphoma, Follicular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D009363:Neoplasm Proteins; D011837:Radiation-Protective Agents; D000069283:Rituximab