Inhibition of Friend erythroleukaemia-cell tumours in vivo by a synthetic analogue of prostaglandin E2

Abstract

Summary.-The effect of 16,16-dimethyl-PGE2-methyl ester (di-M-PGE2), a longacting synthetic analogue of prostaglandin E2, on the replication of Friend erythroleukaemia cells (FLC) in vivo has been studied. Pre-treatment in vitro of both undifferentiated and differentiated FLC with di-M-PGE2 (1 jug/ml) did not alter rates of tumour appearance or growth, but increased the median survival of DBA/2J mice.Systemic administration of di-M-PGE2 (10 1kg/mouse/day) was not toxic to the mice, but significantly inhibited tumour growth and increased median survival in mice injected s.c. with undifferentiated FLC. These effects of di-M-PGE2 were much more pronounced in mice receiving differentiated (DMSO -treated) FLC. In this latter group, the appearance of tumour was also significantly delayed by di-M-PGE2. The different effects of di-M-PGE2 treatment on tumours derived from undifferentiated and differentiated cells suggest that the analogue is acting directly on tumour-cell replication rather than on factors related to the host response.

Treatment of mouse carcinoma in vivo with a prostaglandin E2 analogue and indomethacin

“…This contrasts with the short delay of B16 melanoma appearance in mice given di-me-PGE2 (Santoro et al, 1977;Favalli et al, 1980a), and the slightly faster development of palpable s.c. B16 melanoma tumours with indomethacin (Favalli et al, 1980a).…”

“…Di-me-PGE2 is reported to increase PGE2 formation by Friend erythroleukaemia cells and B-16 melanoma (Santoro et al, 1979;Favalli et al, 1980a). The analogue therefore appears to have a complex action involving an effect on arachidonate release and/or metabolism, as well as stimulation of PGE2 receptors.…”

“…The body weights prior to tumour excision were similar in the mice given di-me-PGE2 and/or indomethacin, and thereafter all the animals looked healthy prior to the development of metastases. Furthermore, others who have used similar doses of the analogue in mice claim that it increases survival in mice with B-16 melanoma (Santoro et al, 1977;Favalli et al, 1980a) and Friend erythroleukaemia (Santoro & Jaffe, 1979).…”

“…In studies using a long-acting analogue of PGE2 (16,16-dimethyl-PGE2 methyl ester; di-me-PGE2) 5 or 10 pg per mouse daily, the size of mouse B16 melanoma was smaller (Santoro et al, 1976(Santoro et al, , 1977 and in some experiments host survival time was longer (Santoro et al, 1977;Favalli et al, 1980a). Other reports on the beneficial effects of PGs on tumours include PGA1 and PGA2 (Honn et al, 1979;Favalli et al, 1980b), PGD2 (Fitzpatrick & Stringfellow, 1979;Sakai et al, 1984), PGF2a (Jubiz et al, 1979) and PGI2 (Honn et al, 1981).…”

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

“…We have previously produced evidence that endogenous PGE is involved in regulating FLC differentiation and proliferation in vitro (Santoro et al, 1979a), and that a PGE2 analogue (16, 16-dimethyl-PGE2-methyl ester; di-M-PGE2) inhibited FLC tumour growth in vivo and increased the survival of mice injected s.c. with FLC (Santoro & Jaffe, 1979). We have also shown that PGA compounds are the most effective PGs for inhibiting FLC proliferation in vitro, and are the only PGs studied that can stimulate differentiation in the absence of other inducers (Santoro et al, 1979b).…”