[Overcoming of ACNU resistance in a subline of rat glioma in vitro and in vivo by reserpine].
Reserpine was shown to enhance the cytotoxicity of ACNU in both C6 and C6/ACNU rat glioma cells in vitro and also to enhance the chemotherapeutic effect of ACNU in C6/ACNU-bearing rats (C6/ACNU meningeal gliomatosis rats), in which ACNU resistance could be partially overcome by reserpine. When reserpine was added to the culture at a concentration of 10 microM, the IC50 of ACNU for C6/ACNU cells decreased to the level of that for C6 cells. Intracellular uptake of ACNU in C6/ACNU cells increased and the efflux from the cells decreased when 20 microM reserpine was added to the culture. In in vivo experiments, combined ACNU (1 mg/kg) and reserpine (250 micrograms/kg) therapy by intrathecal injection of these drugs improved % ILS (increased life span) with statistical significance compared with that after treatment with ACNU alone. The probable explanation of the enhanced cytotoxic-effect of ACNU in ACNU-resistant glioma cells presented in in vitro and in vivo is increased intracellular ACNU concentration resulting from inhibition of the efflux of ACNU from the resistant cells.
Yoshida
T
T
Shimizu
K
K
Ushio
Y
Y
Hayakawa
T
T
Mogami
H
H
Sakamoto
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004351:Drug Resistance; D004357:Drug Synergism; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008577:Meningeal Neoplasms / Q000188:drug therapy*; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; D015376:Nimustine; D012110:Reserpine