A comparison of the modulation of antiblastics cytotoxicity by verapamil and dipyridamole in a human colon carcinoma cell line.
This study was designed to compare the activity of two MDR modulators, verapamil and dipyridamole, on the in vitro growth of a human colon carcinoma cell line. The aims were: a) to investigate the different sensitivity of the parental cell line (LoVo S) and the doxorubicin-resistant one (LoVo R) towards the treatment with several antiblastics and their associations with verapamil or dipyridamole; b) to evaluate if the combined use of these drugs with verapamil or dipyridamole increases their cytotoxicity; c) to understand whether the mechanism of action of each modulator is the same. Idarubicin and vinblastine were the most active drugs on both cell lines. LoVo R cells showed cross-resistance to vinblastine, teniposide and mitoxantrone, while chemosensitivity towards cisplatin and cyclophosphamide was almost the same in both cell lines. The inhibitory effect on cell growth was enhanced when the drugs were associated with verapamil, but no difference was detected with cisplatin and cyclophosphamide. Verapamil is thus an effective MDR modulator when used with drugs actively pumped out of tumour cells by P-glycoprotein, while it is ineffective with drugs that induce resistance by different mechanisms. When combined with dipyridamole, a significant result was observed in the case of cisplatin, where a marked increase of cytotoxicity was detected.
Berti
E
E
Department of Pharmacology Egidio Meneghetti, University of Padova, 35131 Padova, Italy.
Carrara
M
M
Ragazzi
E
E
D'Ancona
S
S
Berti
T
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004176:Dipyridamole / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D015255:Idarubicin / Q000494:pharmacology; D008942:Mitoxantrone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D013713:Teniposide / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D009363:Neoplasm Proteins; D014747:Vinblastine; D004176:Dipyridamole; D004317:Doxorubicin; D003520:Cyclophosphamide; D013713:Teniposide; D008942:Mitoxantrone; D014700:Verapamil; D015255:Idarubicin