The inhibitory effect of the combination of antineoplaston A-10 injection with a small dose of cis-diamminedichloroplatinum on cell and tumor growth of human hepatocellular carcinoma.
The inhibitory effects of a combination of Antineoplaston A-10 Injection with a small dose of cis-diamminedichloroplatinum (CDDP) on cell and tumor growth was tested in vitro and in vivo settings. A human hepatocellular carcinoma cell line (KIM-1) was used for the cell growth and transplanted tumor growth studies. In the cell growth study, one-hour exposure of KIM-1 cells to CDDP in the medium at concentrations of 0.5, 1.0, and 2.0 micrograms/ml inhibited cell growth dose-dependently. Continuous exposure of cultured cells to Antineoplaston A-10 Injection at concentrations of 4, 6, and 8 mg/ml also inhibited tumor growth dose-dependently. The combination of 0.5 microgram/ml CDDP and 6 mg/ml A-10 Injection inhibited cell growth more than did each agent individually. Electron microscopic study showed well-maintained organelle structures in Antineoplaston A-10 Injection-treated cells compared to CDDP-treated cells. alpha-Fetoprotein (AFP) production by 10(4) cells in 48 h increased in the A-10 Injection-treated and A-10 Injection+CDDP-treated groups as the concentration of these agents increased. In the tumor growth study, daily administration of Antineoplaston A-10 Injection 75 mg with once a week administration of 20 micrograms of CDDP for 5 weeks inhibited transplanted tumor growth in athymic mice after 33 days of treatment, while administration of 75 mg of A-10 Injection or 20 or 60 micrograms of CDDP alone showed no significant inhibition of tumor growth.
Tsuda
H
H
Department of Anesthesiology, Kurume University, School of Medicine, Fukuoka-ken.
Sugihara
S
S
Nishida
H
H
Hara
H
H
Eriguchi
N
N
Ishii
K
K
Sasaki
K
K
Yoshimura
S
S
Tanaka
N
N
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D044482:Benzeneacetamides; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010881:Piperidones / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis
D044482:Benzeneacetamides; D010881:Piperidones; D000509:alpha-Fetoproteins; C052091:antineoplaston A10; D002945:Cisplatin