Growth inhibition of Friend erythroleukaemia cell tumours in vivo by a synthetic analogue of prostaglandin A: an action independent of natural killer-activity

S Marini,At Palamara,E Garaci,Mg Santoro

doi:10.1038/bjc.1990.86

Abstract

Prostaglandins of the A series (PGAs) have been previously shown to inhibit the growth and to stimulate the differentiation of Friend erythroleukaemic cells (FLC) in vitro. In the present report we analysed the effect of PGA treatment in vitro on FLC tumorigenicity, and in vivo on FLC proliferation and on natural killer (NK) activity. PGA1 pretreatment of FLC in vitro for 5 days before inoculation into syngeneic mice slightly delayed tumour appearance, but did not significantly alter the pattern of tumour growth or mice survival, indicating that PGA1, at least in the conditions studied, did not affect FLC tumorigenicity. Daily treatment of mice with a long-acting synthetic analogue of PGA2 (16, 16 dimethyl-PGA2-methyl ester, di-M-PGA2) delayed tumour appearance, inhibited tumour growth, as measured by tumour weight and diameter, and increased the median mice survival time by 15-35%, depending on the schedule of treatment. Daily treatment with di-M-PGA2 strongly suppressed NK activity in normal mice but had no significant effect in tumour-bearing immunodepressed mice. PGA treatment of effector or target cells in vitro, or PGA added during the NK assay, had no effect on NK activity. We suggest that the chemotherapeutic effect of PGA is due to a direct action on tumour cell replication rather than to a stimulation of the host NK activity.

Highlights

Friend erythroleukaemia (FLC, strain 745, cell line GM-86 from the Institute for Medical Research, Camden, NJ, USA), K562 erythroleukaemia and YAC-I thymoma cell lines were grown in RPMI 1640 medium (Flow Laboratories, UK), supplemented with 15% fetal calf serum (FCS) or 10% heatinactivated fetal bovine serum (FBS) (Flow Laboratories), respectively for Friend erythroleukaemic cells (FLC) and K562 or YAC-l cells, glutamine 2 mM, penicillin 100 U ml-' and streptomycin 0.1 mg ml' (Complete Culture Medium, CCM), in a humidified 5% CO2 atmosphere at 37°C
If treatment was not repeated after 48 h, in contrast to FLC derived from stationary-phase cultures, these cells regained their growth potential and no significant inhibition of cell proliferation was found after 96 h of Prostaglandins of the A series (PGAs), treatment
The rate of tumour appearance, the pattern of tumour growth and mouse survival rate were compared with those of mice injected with untreated FLC