奥曲肽和NC-8-12对人结肠癌细胞株HCT116体内外生长的影响

Effects of Octreotide and NC-8-12 on the Proliferation of Human Colonic Carcinoma Cell Line HCT116 in vitro and in vivo

目的 探讨生长抑素类似物 (SSTA)能否在体内、外抑制结肠癌细胞的增殖及其抑制作用的可能机理。方法 用RT PCR和原位杂交方法检测人结肠癌细胞株HCT116生长抑素Ⅱ型受体 (SSTR2 )mRNA的表达 ;用MTT法检测奥曲肽 (Oct)或SSTR2特异激动剂NC 8 12对胰岛素或表皮生长因子刺激下的HCT116细胞作用2 4h后的增殖情况 ,并用流式细胞仪检测其CyclinD1的表达 ;同时将HCT116细胞种植于裸鼠皮下 ,给予其奥曲肽或NC 8 12治疗 ,观察肿瘤生长情况。结果 ①HCT116细胞株和荷瘤裸鼠癌组织中均有SSTR2mRNA的表达 ;②胰岛素和表皮生长因子能促进HCT116细胞株生长 ,且这一促进作用能部分地被Oct和NC 8 12减弱 ;③胰岛素刺激下HCT116细胞的CyclinD1表达水平提高 ,Oct或NC 8 12作用后其表达水平下降 ,但差异无显著性意义 (P>0 .0 5 ) ;④Oct和NC 8 12组裸鼠皮下种植瘤重量和体积与对照组比较差异无显著性意义 (P>0 .0 5 )。结论 在体外 ,Oct及NC 8 12均能抑制HCT116细胞株增殖 ,SSTR2参与介导了SSTA抑制结肠癌细胞生长的作用 ;在本实验剂量下 ,Oct和NC 8 12均对接种于裸鼠的人结肠癌肿瘤生长无影响。

Objective To investigate the inhibitory effects of somatostatin analogue (SSTA) on the colonic carcinoma cell growth in vitro and in vivo and its possible mechanism. Methods The somatostatin receptor type Ⅱ (SSTR2) mRNA of colonic carcinoma cell line HCT116 was detected by using RT PCR and hybridization in situ . The effects of octreotide (Oct) or NC 8 12 (specific agonist of SSTR2 ) on the proliferation of HCT116 was measured with MTT after HCT116 stimulated by insulin or epidermal growth factor (EGF) and incubated with Oct or NC 8 12 simultaneously for 24 hours. The expression of cyclin D1 was detected with flow cytometry. The HCT116 were implanted in nude mice subcutaneously and treated with Oct or NC 8 12. The tumor volume and tumor weight were measured according to schedule. Results ①SSTR2 mRNA was detected in HCT116 and the tumor implanted in nude mice; ②Insulin and EGF increased the proliferation of HCT116 significantly, and this proliferation could be inhibited by Oct and NC 8 12 partially; ③Insulin increased the Cyclin D1 expression of HCT116, its level decreased slightly when treated with Oct or NC 8 12 but not significantly ( P >0.05); ④The weight and volume of implanted tumor in nude mice treated with Oct or NC 8 12 showed no significant difference compared with the control group ( P >0.05). Conclusion Both Oct and NC 8 12 could inhibit the proliferation of colonic carcinoma cell line HCT116 in vitro , which indicated that SSTR2 may mediated the inhibition. Oct and NC 8 12 have no effect on the growth of implanted HCT116 in nude mice in this experiment.