The effects of anticancer drugs in combination with nimodipine and verapamil on cultured cells of glioblastoma multiforme.
The presence of the cellular multidrug resistance (MDR1) gene and its product, P-glycoprotein (Pgp), is thought to be a mechanism for the failure of chemotherapy in cancer patients. Calcium channel blockers have been shown to sensitise cancer cells to anticancer drugs by reversing Pgp expression in cell lines. The interactions between anticancer drugs such as carmustine (BCNU), vincristine (VCR) and procarbazine (PCB) and calcium channel blockers such as nimodipine and verapamil on cultured cells of glioblastoma from eight patients were therefore tested. Pgp expression was examined immunohistochemically using C219 monoclonal antibody in cytospin preparation. The cytotoxicity of the drugs was screened using microculture tetrazolium assay. The cells from five patients showed positive immunoreaction for Pgp. Nimodipine showed growth-inhibitory activity against glioblastoma cells at a rate of 16.55-26.88% (P < 0.05), but a similar effect was not observed with verapamil. While antiproliferative effects of BCNU were around 20.91-45.09% (P < 0.05) on the cells from seven patients, VCR was the most effective agent in inhibition of cell growth at a rate of 26.43-48.47% (P < 0.05). The response of the cells from five patients to PCB was from 11.98 to 16.32% (P < 0.05). When used together, nimodipine further enriched cytotoxicity of the anticancer drugs up to 11.14-40.85% (P < 0.05) without relation to Pgp expression. In conclusion, the enhancement of cytotoxicity of anticancer drugs by nimodipine suggests that there might be a synergy between anticancer drugs and nimodipine in the inhibition of glioma cell growth.
Durmaz
R
R
Department of Neurosurgery, Medical Faculty, Osmangazi University, Eskişehir, Turkey. rdurmaz@ogu.edu.tr
Deliorman
S
S
Uyar
R
R
Işiksoy
S
S
Erol
K
K
Tel
E
E
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002330:Carmustine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D009553:Nimodipine / Q000494:pharmacology*; D011344:Procarbazine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D011344:Procarbazine; D009553:Nimodipine; D014750:Vincristine; D014700:Verapamil; D002330:Carmustine