Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumour growth by non-steroidal anti-inflammatory drugs

Abstract

Summary.-Prostaglandin (PG) E2 biosynthesis in Yoshida hepatoma (AH 130) was evaluated by radioimmunoassay. When hepatoma cells were incubated in vitro, the levels of PGE2 in the medium were similar to those found in hepatocytes for the first 2 h; this was followed by a rapid increase in PGE2 formation, and the 6h incubation levels were 4-fold higher than in hepatocytes.Addition of sodium arachidonate markedly and dose-dependently stimulated PGE2 synthesis; the increase was largely prevented by the addition of indomethacin (1 um) or L 8027, a prostaglandin synthetase inhibitor.Experiments in vivo indicated that indomethacin treatment of tumour-bearing rats significantly reduced the tumour mass. When rats were injected with PGE2 after receiving the drug, the number of tumour cells was very similar to that of untreated animals. This, as well as the inhibition of tumour growth by acetylsalicylic acid, strongly suggests that the inhibition of PG biosynthesis by antiinflammatory drugs and the inhibition of tumour proliferation may be closely associated events. It was also found that injections of indomethacin very significantly prolonged survival of hepatoma-bearing rats. Since PGE2 does not appear to affect the cyclic AMP levels of hepatoma cells, it is possible that hepatoma may use PGE2 to subvert the immune system. This could help to explain the effectiveness of anti-inflammatory drugs in the control of tumour growth.

Humoral mediation for cachexia in tumour-bearing rats

“…By contrast, the release of IL-1 was not affected, either in the presence or in the absence of LPS (Table II). As for the alternative hypothesis, the AH-130 hepatoma cells released appreciable amounts of PGE2 (Figure 6), in agreement with previous reports (Strelkov et al, 1989;Trevisani et al, 1980;also see Tanaka et al, 1989). Of special interest was the finding that in short-term culture these tumour cells released significant amounts of TNF as well as of IL-1 (Figure 6).…”

Increased survival of cancer-bearing mice treated with inhibitors of prostaglandin synthesis alone or with chemotherapy

“…The increased survival after tumour excision also agrees with some other studies using INDO alone (Lynch et al, 1978;Trevisani et al, 1980). However, in contrast to our previous results (Bennett et al, 1978Berstock et al, 1979) Since INDO and FLU are both potent inhibitors of prostaglandin synthesis (as confirmed by us) the overall similarity of their anticancer effects strengthens the possibility that prostaglandins are involved.…”

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

“…In contrast, several groups have found that PG synthesis inhibitors reduce mouse tumour weight (Hial et al, 1976;Bennett et al, 1978Bennett et al, , 1979Bennett et al, , 1982Lynch et al, 1978;Lynch & Salomon, 1979;Trevisani et al, 1980), and increase host survival (Lynch et al, 1978;Bennett et al, 1978Bennett et al, , 1979Bennett et al, , 1982Trevisani et al, 1980). In a few studies PG synthesis inhibitors were not of value, indicating that different tumour types may vary in their response (see Bennett, 1982).…”