Fisher W E, Muscarella P, Boros L G, Schirmer W J
Department of Surgery, Ohio State University, Columbus 43210, USA.
Surgery. 1998 Mar;123(3):315-20.
Streptozotocin-diabetes prevents induction of pancreatic tumors in several animal models and inhibits the growth of established human pancreatic cancer implants in nude mice. However, it also promotes growth of the hamster pancreatic cancer cell line, H2T, in the Syrian hamster. To test the hypothesis that these contradictory effects are due to tumor host differences, the growth of the H2T cell line was examined in the streptozotocin-diabetic nude mouse.
H2T cells were implanted subcutaneously into streptozotocin-diabetic nude mice (n = 10) and untreated control mice (n = 10). After 21 days, tumors were excised and weighed. Plasma insulin and somatostatin were determined by radioimmunoassay.
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 animals (insulin, 23 microU/ml vs 31 microU/ml; p < 0.001). In contrast, somatostatin was significantly elevated in the streptozotocin-diabetic group compared with the control group (somatostatin, 179 pg/ml versus 54 pg/ml, p < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd, 15.5 nmol/L), and somatostatin (Kd, 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%).
The variable effect of streptozotocin-diabetes on pancreatic cancer growth is due to differences in the tumor host. The growth of pancreatic cancer, particularly in streptozotocin-diabetic nude mice, may be influenced by gut peptides in a receptor-dependent fashion.
链脲佐菌素诱导的糖尿病可预防多种动物模型中胰腺肿瘤的发生，并抑制裸鼠体内已形成的人胰腺癌移植瘤的生长。然而，它也能促进叙利亚仓鼠体内仓鼠胰腺癌细胞系H2T的生长。为了验证这些相互矛盾的作用是由于肿瘤宿主差异所致的假说，我们检测了链脲佐菌素诱导糖尿病的裸鼠体内H2T细胞系的生长情况。
将H2T细胞皮下植入链脲佐菌素诱导糖尿病的裸鼠（n = 10）和未处理的对照小鼠（n = 10）体内。21天后，切除肿瘤并称重。采用放射免疫分析法测定血浆胰岛素和生长抑素水平。
3周后，对照组肿瘤重量为118 mg，糖尿病组肿瘤重量为28 mg（p < 0.001）。与对照动物相比，链脲佐菌素处理的动物血浆胰岛素水平显著降低（胰岛素，23 μU/ml对31 μU/ml；p < 0.001）。相反，与对照组相比，链脲佐菌素诱导糖尿病组的生长抑素水平显著升高（生长抑素，179 pg/ml对54 pg/ml，p < 0.001）。竞争性结合研究显示，H2T细胞表面存在胰岛素特异性细胞表面受体（解离常数Kd，15.5 nmol/L）和生长抑素特异性细胞表面受体（Kd，2.5 nmol/L）。在体外细胞增殖试验中，胰岛素可促进细胞分裂（p < 0.01，最大增幅为+11%），而生长抑素则抑制细胞分裂（p < 0.01，最大降幅为-18%）。
链脲佐菌素诱导的糖尿病对胰腺癌生长的影响存在差异，这是由于肿瘤宿主的差异所致。胰腺癌的生长，尤其是在链脲佐菌素诱导糖尿病的裸鼠中，可能以受体依赖的方式受到肠道肽的影响。
