Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of murine neuroblastoma in vivo.
Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of two murine neuroblastomas (C1300, NS-20) was investigated in vivo. Five groups of mice were prepared; group 1 were fed the control diet, group 2 were fed a vitamin E-deficient diet, group 3 were fed a vitamin E-supplemented diet, group 4 were fed the control diet and plus vitamin E solution given intraperitoneally during the treatment (solvent i.p. group), and group 5 were given vitamin E in the same manner (20 mg/kg/day; vitamin E i.p. group). Cisplatin (6 mg/kg) was injected intraperitoneally into the mice of each group during the treatment. In case of the C1300 neuroblastoma, the antitumor activity of cisplatin was most enhanced in the mice receiving vitamin E i.p., and the intra-tumor vitamin E and platinum levels were significantly higher in this group than in the other groups (P less than 0.01, and P less than 0.05 respectively). In contrast, in animals transplanted with the NS-20 murine neuroblastoma, which proved to be a cisplatin-tolerant tumor in separate experiments, no combined effect of those drugs was observed, although the intra-tumor level of platinum was elevated. The possibility was that vitamin E increases the influx of cisplatin into the tumor cells and acts after incorporation of cisplatin through the plasma membrane. Vitamin E did not accentuate the cisplatin-induced renal impairment in vitamin E-loaded groups. Those results suggested that vitamin E should be considered as a co-agent of cisplatin for the treatment of neuroblastoma.
Sue
K
K
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University 60, Fukuoka, Japan.
Nakagawara
A
A
Okuzono
S
S
Fukushige
T
T
Ikeda
K
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D010984:Platinum / Q000378:metabolism; D013997:Time Factors; D014810:Vitamin E / Q000008:administration & dosage / Q000378:metabolism
D014810:Vitamin E; D010984:Platinum; D002945:Cisplatin