Acidic and neutralized metoclopramide formulations sensitize ionizing radiation induced cytotoxicity in a human lung adenocarcinoma xenografted to scid mice.
A neutralized formulation (Neu-Sensamide) of metoclopramide (MCA) has been shown to possess reduced sedative side effects compared with the conventional acidic formulations (Primperan). The acidic formulation of MCA has also been shown to sensitize the effect of ionizing radiation (6-8 Gy) using human squamous cell carcinomas from the head and neck xenografted to nude mice. In the present study, 2 mg MCA/kg body weight 1-3 h before treatment with 1 Gy radiation (single dose) was evaluated in scid mice xenografted with a human lung adenocarcinoma. MCA given alone in acidic or neutralized formulations did not show any effect on tumor growth retardation. However, when combined with radiation, both acidic and neutralized formulations of MCA sensitized the cytotoxic effect of radiation directed against the tumors by increasing tumor doubling time, tumor quadrupling time and specific growth delay, and by decreasing area under growth curve measurements. In addition, there was no statistically significant difference between the two formulations of MCA in the efficacy of sensitizing the cytotoxicity of a single low dose (1 Gy) of radiation.
Hua
J
J
Department of Molecular Ecogenetics, Wallenberg Laboratory, University of Lund, Sweden.
Olsson
A
A
Sheng
Y
Y
Pero
R W
RW
D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008787:Metoclopramide / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000633:toxicity; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D008787:Metoclopramide