Upp J R, Olson D, Poston G J, Alexander R W, Townsend C M, Thompson J C
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Am J Surg. 1988 Jan;155(1):29-35. doi: 10.1016/s0002-9610(88)80254-x.
Somatostatin inhibits hormone secretion from gastrointestinal endocrine tumors. The purpose of this study was to determine whether SMS 201-995, a long-acting analog, would inhibit the growth of pancreatic adenocarcinomas. Two human pancreatic cancers grown in nude mice were studied: SKI, which has cholecystokinin receptors, and CAV, which does not. Tumors were implanted in groups of six mice each. Treatment groups received SMS 201-995 (100 micrograms/kg three times daily) by intraperitoneal injections and control animals received saline solution. Tumor area was measured twice weekly. After 7 weeks, the tumors and mouse pancreases were excised, weighed, and analyzed for protein and RNA and DNA content. In a second set of experiments, treatment was begun 21 days after transplantation. Mean body weights between groups were not different in any experiment. With treatment beginning on the day of transplantation, the tumor areas of SKI and CAV cancers were reduced by the third and fifth weeks of treatment, respectively. Tumor doubling times were prolonged with treatment in both SKI tumors (5 days) and CAV tumors (6 days). In the SKI treatment groups, tumor weight (52 percent), RNA content (72 percent), and DNA content (60 percent) were decreased at sacrifice compared with those of the control groups. In the CAV treatment group, the mean tumor weight (55 percent) and protein (48 percent), RNA (67 percent) and DNA contents (60 percent) were decreased compared with the CAV control group. Tumor growth of SKI and CAV cancers was also inhibited when treatment was delayed 21 days after transplantation. We conclude that these effects are not mediated by inhibition of cholecystokinin, as seen by similar inhibitory effects on both tumors. Treatment with SMS 201-995 may be an effective hormonal therapy in patients with pancreatic cancers.
生长抑素可抑制胃肠内分泌肿瘤的激素分泌。本研究旨在确定长效类似物SMS 201-995是否会抑制胰腺腺癌的生长。对在裸鼠体内生长的两种人类胰腺癌进行了研究：具有胆囊收缩素受体的SKI和不具有该受体的CAV。将肿瘤植入每组六只小鼠体内。治疗组通过腹腔注射接受SMS 201-995（每日三次，每次100微克/千克），对照组动物接受生理盐水。每周两次测量肿瘤面积。7周后，切除肿瘤和小鼠胰腺，称重，并分析蛋白质、RNA和DNA含量。在第二组实验中，移植后21天开始治疗。在任何实验中，各组之间的平均体重均无差异。在移植当天开始治疗时，SKI和CAV癌的肿瘤面积分别在治疗的第三周和第五周减小。治疗使SKI肿瘤（5天）和CAV肿瘤（6天）的肿瘤倍增时间延长。在SKI治疗组中，与对照组相比，处死时肿瘤重量（52%）、RNA含量（72%）和DNA含量（60%）均降低。在CAV治疗组中，与CAV对照组相比，平均肿瘤重量（55%）、蛋白质（48%）、RNA（67%）和DNA含量（60%）均降低。移植后延迟21天开始治疗时，SKI和CAV癌的肿瘤生长也受到抑制。我们得出结论，这些作用并非通过抑制胆囊收缩素介导，因为在两种肿瘤上均观察到类似的抑制作用。用SMS 201-995治疗可能是胰腺癌患者一种有效的激素治疗方法。
