Experimental studies on the treatment of hepatocellular carcinoma with cis-platin.transferrin complex.
Using several tumor cell lines (HC-32, C-Hc4 and MHT-1), the anti-proliferating action of cis-dichlorodiamine platinum (cis-platin) was investigated in relation to the transferrin receptors (Tf-R) expressed on the surface of these cell lines. The number of Tf-R determined by 131I-transferrin binding assay was the most in HC-32, the least in C-Hc 4 and intermediate in MHT-1. Cis-platin was found to bind stoichiometrically to transferrin and to produce more marked inhibition of 3H-thymidine uptake in the presence of apo-transferrin, suggesting that cis-platin.transferrin complex was transferred into the cells through Tf-R. Cis-platin itself increased the binding sites of transferrin. Insulin, known to cause redistribution of Tf-R to the cell surface, potentiated the inhibition of 3H-thymidine uptake induced by cis-platin and apotransferrin in the concentrations less than 50 nM. Furthermore, insulin was found to increase the binding sites of transferrin in Hc-32 in the concentrations less than 5 nM. These facts support that cis-platin was effectively transferred into the cells through Tf-R, when apotransferrin coexisted with cis-platin. Some [Ca2+]0 and protein kinase C (PK-C) modulators affected Tf-R turnover in these cell lines. These results suggested the possibility that a combination treatment of cis-platin.transferrin complex with insulin or [Ca2+]0 and/or PK-C modulators may not only enhance the antiproliferating effect of cis-platin, but also reduce the dose of cis-platin.
Hamada
Y
Y
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000494:pharmacology; D011990:Receptors, Transferrin / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology*
D007328:Insulin; D011990:Receptors, Transferrin; D014168:Transferrin; D011493:Protein Kinase C; D002945:Cisplatin; D002118:Calcium