[Enhancement of anti-tumor effect of adriamycin by verapamil in a intrahepatic arterial infusion in the rats].
In a intrahepatic arterial infusion, the enhancement of cytotoxicity of adriamycin (ADR) by verapamil (VER), a calcium antagonist was investigated in male Wistar rat with liver tumor of Walker 256 carcinosarcoma. The accumulation of ADR in tumor tissue at 2 hrs after a bolus intrahepatic arterial injection of ADR with VER (4 mg/kg) was 1.9-fold more than without VER. But VER did not enhance it in normal liver tissue and heart tissue. In the continuous intrahepatic arterial infusion therapy (cia) of ADR and VER (1.5 mg/kg/day) for 6 days, tumor weight and the accumulation of ADR in tumor tissue, normal liver tissue and heart tissue were assessed. Tumor weight of ADR-cia+VER-cia group was significantly less than ADR-cia group (p less than 0.05). And the accumulation of ADR in tumor tissue of ADR-cia+VER-cia group was significantly higher than ADR-cia group (p less than 0.05). But VER did not enhance it in normal tissue. The administration of VER in a intrahepatic arterial infusion is shown to be able to enhance the cytotoxicity of ADR in tumor tissue but not to enhance in normal tissue. The continuous intrahepatic arterial infusion of VER enhanced cytotoxicity of ADR at clinical dose and it suggests the clinical applicability of VER in cancer chemotherapy.
Shimoda
T
T
First Department of Surgery, Chiba University School of Medicine, Japan.
Miyazaki
M
M
Utagawa
I
I
Koshikawa
H
H
Ito
H
H
Okui
K
K
D000818:Animals; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014700:Verapamil / Q000008:administration & dosage / Q000627:therapeutic use*
D004317:Doxorubicin; D014700:Verapamil