INHIBITORY EFFECT OF THE SOMATOSTATIN ANALOG SMS-201-995 AND CYTOKINES ON THE PROLIFERATION OF HUMAN COLON ADENOCARCINOMA CELL-LINES

The activity of the synthetic somatostatin analogue SMS 201-995 was in vestigated in vitro on the growth of SW480 and SW620 human colon adeno carcinoma cell lines. The inhibition of cell proliferation was signifi cant in SW480 cells (-19.6+/-1.4% at SMS 201-995 10(-9) M, P<0.05), bu t not in SW620 cells (-5.5+/-0.8% at SMS 201-995 10(-8) M) as compared to untreated cultures, Moreover, SMS 201-995 10(-8) M decreased the m itogenic effect of epidermal growth factor (EGF) on the SW480 cell lin e (-26.6+/-3.4% vs. cells exposed to EGF 10 ng ml(-1) alone, P<0.05). The effect of combining SMS 201-995 plus the cytokines interleukin-2 ( IL-2) or gamma-interferon (gamma-IFN) on SW480 and SW620 cancer cell g rowth was also evaluated. The treatment produced a synergistic antipro liferative effect against SW620 cells as compared to untreated culture s, with growth inhibition being -20.2+/-1.2 and -19.3+/-1.3%, at SMS 2 01-995 10(-8) M plus IL-2 or gamma-IFN 100 IU ml(-1), respectively, bu t did not increase the activity of SMS 201-995 against the SW480 cells . In conclusion, the effect of SMS 201-995 on colon cancer cell growth can be enhanced by its combination with cytokines in SW620 but not in SW480 colon adenocarcinoma cells. (C) 1995 The Italian Pharmacologica l Society