Poston G J, Townsend C M, Rajaraman S, Thompson J C, Singh P
Department of Surgery University of Texas Medical Branch, Galveston 77550.
Pancreas. 1990 Mar;5(2):151-7. doi: 10.1097/00006676-199003000-00005.
We studied the effects of SMS 201-995 (SMS), a somatostatin analog, and tamoxifen, an antagonist of estrogenic actions, on the growth of human pancreatic cancers (SKI and PGER) in vivo. Male nude mice were inoculated with either SKI or PGER by passage of tumor chunks (3 mm2) to the scapular region. Mice from each tumor group were randomly allocated to one of four treatment groups: group 1, control group; group 2, SMS (100 micrograms/kg t.i.d.); group 3, tamoxifen (10 mg/kg three times a week); and group 4, SMS (100 micrograms/kg t.i.d.) + tamoxifen (10 mg/kg three times a week). The somatostatin analog, SMS, given alone or as a combined regimen with tamoxifen, significantly reduced (a) the rate of growth of SKI, and (b) DNA, RNA, and protein content of the tumors. On the other hand, in the case of PGER tumors, none of the treatment regimens significantly influenced the growth of PGER in vivo. Despite showing no significant effects during the study, PGER tumors in mice receiving tamoxifen alone had significantly lower total DNA, RNA, and protein contents compared to control tumors; this was reversed on combined treatment with SMS. None of the growth parameters of PGER was effected by SMS alone. We conclude that, in the case of SKI, SMS with or without tamoxifen was effective as a growth inhibitory agent, whereas in the case of PGER, tamoxifen alone was effective. This finding suggests that independent pathways mediate the growth-inhibitory effects of tamoxifen and SMS, and that different pancreatic cancers may respond to the two agents differently, some with inhibition, some not.
我们研究了生长抑素类似物SMS 201-995(SMS)和雌激素作用拮抗剂他莫昔芬对人胰腺癌(SKI和PGER)体内生长的影响。将肿瘤块(3平方毫米)接种到雄性裸鼠肩胛区域,使其感染SKI或PGER。每个肿瘤组的小鼠被随机分配到四个治疗组之一:第1组,对照组;第2组,SMS(100微克/千克,每日三次);第3组,他莫昔芬(10毫克/千克,每周三次);第4组,SMS(100微克/千克,每日三次)+他莫昔芬(10毫克/千克,每周三次)。单独给予生长抑素类似物SMS或与他莫昔芬联合用药,均能显著降低(a)SKI的生长速率,以及(b)肿瘤的DNA、RNA和蛋白质含量。另一方面,对于PGER肿瘤,这些治疗方案均未对其体内生长产生显著影响。尽管在研究期间未显示出显著效果,但单独接受他莫昔芬治疗的小鼠体内PGER肿瘤的总DNA、RNA和蛋白质含量显著低于对照肿瘤;与SMS联合治疗后这种情况得到逆转。单独使用SMS对PGER的任何生长参数均无影响。我们得出结论,对于SKI,无论有无他莫昔芬,SMS都可作为生长抑制剂发挥作用;而对于PGER,单独使用他莫昔芬有效。这一发现表明,他莫昔芬和SMS的生长抑制作用由独立的途径介导,不同的胰腺癌对这两种药物的反应可能不同,有些受到抑制,有些则不受影响。