Does verapamil help overcome multidrug resistance in tumor cell lines and cancer patients?
The aim of these experimental and clinical studies was to determine if verapamil helps overcome multidrug resistance in tumor cells and in cancer patients. The effect of the calcium channel blocker verapamil on the antiproliferative activity of epirubicin (Farmorubicin, Farmitalia) was followed up in in vitro studies on two constant human leukemia cell lines: CEM/O (P-gp negative) and CEM/VCR 1000 with a positive multidrug resistant (MDR) phenotype. The MTT assay was used to study the antiproliferative activity. Verapamil in concentrations of 3 and 10 micrograms/ml enhanced by 10-fold and 19-fold, respectively, the effect of epirubicin in CEM/VCR 1000 cells and had no significant effect on epirubicin activity in CEM/O. Eleven patients with measurable stage IV breast cancer, clinically resistant to anthracycline treatment, received the FEC combination (5-fluorouracil-epirubicin-cyclophosphamide) twice with verapamil pretreatment, p.o. at the doses of 1280-2560 mg. There were two complete remissions (soft tissue metastases), four partial remissions (soft tissue metastases and lung metastases), and three stable diseases. These studies confirm the possibilities of overcoming multidrug resistance by the administration of verapamil in tumor cells and in cancer patients.
Timcheva
C V
CV
Chemotherapy Department, National Center of Oncology, Sofia, Bulgaria.
Todorov
D K
DK
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004359:Drug Therapy, Combination; D015251:Epirubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000009:adverse effects / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D002121:Calcium Channel Blockers; D015251:Epirubicin; D014700:Verapamil