Ning Shoucheng, Knox Susan J, Harsh Griffith R, Culler Michael D, Katznelson Laurence
Department of Radiation Oncology, Stanford University School of Medicine, Stanford University Medical Center, 875 Blake Wilbur Drive, Stanford, California 94305-5821, USA.
Endocr Relat Cancer. 2009 Sep;16(3):1045-55. doi: 10.1677/ERC-09-0003. Epub 2009 Jun 15.
Somatostatin analogs are a mainstay of medical therapy in patients with GH producing human pituitary tumors, and it has been suggested that somatostatin analogs may be radioprotective. We utilized GH secreting rat GH3 cells to investigate whether a somatostatin analog may limit the effects of radiation on proliferation and apoptosis in vitro and on tumor growth in vivo. Treatment with lanreotide alone at doses of either 100 or 1000 nM for 48 h reduced clonogenic survival by 5-10%. Radiation alone produced a dose-dependent survival curve with a SF2 of 48-55%, and lanreotide had no effect on this curve. The addition of lanreotide resulted in a 23% increase in the proportion of apoptotic sub-G1 cells following irradiation (P<0.01). In a mouse GH3 tumor xenograft model, lanreotide 10 mg/kg moderately inhibited the growth of GH3 tumors, with a 4x tumor growth delay (TGD) time that ranged from 4.5 to 8.3 days. Fractionated local tumor radiation alone significantly inhibited tumor growth and produced a TGD of 35.1+/-5.7 days for 250 cGy fractions. The combination of lanreotide, either antecedent to or concurrent, with radiation of 250, 200 or 150 cGy/fraction for 5 days inhibited tumor growth and produced the TGD times that were similar to radiation alone (P>0.05). Pretreatment with lanreotide had the most significant radiosensitizing effect. These studies demonstrate that the somatostatin analog lanreotide is not radioprotective in GH3 cells, and further studies are necessary to determine the impact of lanreotide on apoptosis.
生长抑素类似物是治疗人类生长激素分泌型垂体肿瘤患者的主要药物，并且有人提出生长抑素类似物可能具有辐射防护作用。我们利用分泌生长激素的大鼠GH3细胞来研究生长抑素类似物是否可以在体外限制辐射对细胞增殖和凋亡的影响以及在体内限制辐射对肿瘤生长的影响。单独使用剂量为100或1000 nM的兰瑞肽处理48小时可使克隆形成存活率降低5 - 10%。单独辐射产生了剂量依赖性存活曲线，其SF2为48 - 55%，而兰瑞肽对此曲线无影响。添加兰瑞肽导致照射后凋亡的亚G1期细胞比例增加23%（P<0.01）。在小鼠GH3肿瘤异种移植模型中，10 mg/kg的兰瑞肽适度抑制了GH3肿瘤的生长，肿瘤生长延迟（TGD）时间为4.5至8.3天，延长了4倍。单独分次局部肿瘤辐射显著抑制肿瘤生长，对于250 cGy分次照射产生的TGD为35.1±5.7天。兰瑞肽在辐射前或同时与250、200或150 cGy/分次的辐射联合使用5天，抑制了肿瘤生长，产生的TGD时间与单独辐射相似（P>0.05）。兰瑞肽预处理具有最显著的放射增敏作用。这些研究表明，生长抑素类似物兰瑞肽在GH3细胞中不具有辐射防护作用，需要进一步研究以确定兰瑞肽对凋亡的影响。
