[Overcoming of ACNU resistance in an ACNU-resistant subline of rat C6 glioma in vivo through enhanced effect of ACNU by calmodulin inhibitor].
A calmodulin inhibitor, trifluoperazine, was found to enhance the cytotoxic action of ACNU in C6, especially in ACNU-resistant (C6/ACNU) glioma cells in vitro. In order to clarify the efficacy of trifluoperazine in vivo, 1 X 10(7) C6 or C6/ACNU cells were percutaneously implanted into the cisterna magna of Wistar rats to produce meningeal gliomatosis (MG) models as a chemosensitivity assay system. MG rats were treated with ACNU and trifluoperazine according to a variety of schedules. Trifluoperazine in doses of 250 to 500 micrograms/kg intrathecally (it) administered with 1 mg/kg ACNU 1 day after the tumor inoculation significantly increased the life span of the C6/ACNU bearing (C6/ACNU MG) rats. At doses of 250 and 500 micrograms/kg of trifluoperazine in the C6/ACNU MG rats, values of increased life span of 22 and 30% were obtained with a 1 mg/kg dose of ACNU, respectively. These values were statistically significant compared with that obtained in the C6/ACNU MG rats treated with ACNU alone at 1 mg/kg. It might be concluded that the combination chemotherapy with ACNU and such a calmodulin inhibitor as trifluoperazine could overcome ACNU resistance in malignant brain tumors.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D004351:Drug Resistance; D005910:Glioma / Q000188:drug therapy*; D008297:Male; D015376:Nimustine; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D002147:Calmodulin; D009607:Nitrosourea Compounds; D015376:Nimustine; D014268:Trifluoperazine