VARIABLE EFFECT OF STREPTOZOTOCIN-DIABETES ON THE GROWTH OF HAMSTER PANCREATIC-CANCER (H2T) IN THE SYRIAN-HAMSTER AND NUDE-MOUSE

Background, Streptozotocin-diabetes prevents induction of pancreatic t umors in several animal models and inhibits the growth of established human pancreatic cancer implants in nude mice. However, it also promot es growth of the hamster pancreatic cancer cell line H2T: in the Syria n hamster To test the hypothesis that these contradictory effects are due to tumor host differences, the growth of the H2T cell line was exa mined in the streptozotocin-diabetic nude mouse.Methods, H2T cells wer e implanted subcutaneously into streptozotocin-diabetic nude mice (n = 10) and untreated control mice (n = 10). After 21 days, tumors were e xcised and weighed. Plasma insulin and somatostatin were determined by radioimmunoassay. Results. After 3 weeks, tumors in the control group weighed 118 mg and tumors in the diabetic group weighed 28 mg (p < 0. 001). Plasma insulin was significantly decreased in the streptozotocin -treated animals compared with control animal (insulin 23 mu U/ml vs 3 1 mu U/ml; p < 0.001). In contrast, somatostatin was significantly ele vated in the streptozotocin-diabetic group compared with the control g roup (somatostatin, 179 pg/ml versus 54 pg/ml, p < 0.001). Competitive binding-studies revealed specific cell surface receptors for insulin (K-d, 15.5 nmol/L, and somatostatin (K-d, 2.5 nmol/L) on the H2T cells . In an in vitro cell proliferation assay, cell division was promoted by insulin (p < 0.01, maximum +11%) and inhibited by somatostatin (P < 0.01, maximum -18%). Conclusions, The variable effect of streptozotoc in-diabetes on pancreatic cancer growth is due to differences in the t umor host. The growth of pancreatic cancer, particularly in streptozot ocin-diabetic nude mice, may Be influenced by gut peptides in a recept or-dependent fashion.