生长抑素类似物对人胃癌细胞生长的调控作用*

目的：研究奥曲肽对SGC 7901生长的调控作用并探讨其作用的机理。方法：奥曲肽作用体外培养的SGC 7901，5-FU 作为阳性对照，人成纤维细胞作为正常对照，通过MTT 法观察奥曲肽对SGC 7901和成纤维细胞生长的抑制作用，并与5-FU 的抑制作用比较；用荧光显微镜观察细胞凋亡的变化；用流式细胞术分析奥曲肽对胃癌细胞周期分布及凋亡率的影响；用放射免疫法测定胃癌细胞培养液中IGF-1 的含量。结果：奥曲肽50μ g/L 时对胃癌细胞的生长无抑制作用（P>0.05），随着浓度的增加，抑制作用逐渐增强，有量效依赖关系（P<0.01）；各组奥曲肽对人成纤维细胞的生长抑制无明显差异（P>0.05）；500 μ g/L 浓度的奥曲肽对细胞的抑制率与50mg/L5-FU 对细胞的抑制率无统计学意义（P>0.05）；经1mg/L奥曲肽作用 48h 后发生明显的细胞凋亡的形态学变化；SGC 7901细胞经 500 μ g/L奥曲肽作用后，大部分细胞被阻滞于G0/G1 期（72.07± 2.40），S 期细胞明显减少（14.99± 1.42），细胞增殖明显受到抑制，凋亡率增加（21.40± 2.71）；经不同浓度奥曲肽处理后，细胞培养液中IGF-1 含量低于对照组（P<0.01），提示奥曲肽具有下调细胞培养体系中IGF-1 含量的作用。结论：奥曲肽可在体外抑制胃癌细胞的增殖，对非靶细胞的生长无明显的抑制作用。奥曲肽可通过诱导胃癌细胞出现G0/G1 期阻滞和细胞凋亡直接抑制细胞生长，并可抑制IGF 生长因子的分泌，间接抑制肿瘤细胞的生长。

The Ragulatory Effect of Somatostatin on the Growth of Gastric Carcinoma Cell Line

Objective:To study the regulatory effect of somatostatin analogue octreotide on human gastric cancer cell line SGC7901 and to explore the corresponding mechanisms.Methods:Moderately differentiated human gastric carcinoma SGC-7901 cells were treated with octreotide in vitro.SGC-7901 cells treated with 5-FU were the positve controls and human fibroblasts were the normal controls.MTT assay was used to observe the inhibitory effect of octreotide on human gastric carcinoma cells and human fibroblasts.We observed the apoptosis through fluorescent microscope.The influence of octreotide on cell cycle distribution and the apoptosis rate of human gastric carcinoma cell were analyzed with FCM.Radiommunoassay was employed to determine the changes in IGF-1 levels in cell culture fluid.Results:Octretide can not inhibit the growth of gastric cells at low concentration(50ug/L).With the increase of octretide concentration,the inhibitory effect increased gradually,in a dose-dependent manner.Octretide had an evident inhibitory effect on human fibroblasts(P>0.05).There was no difference in the inhibition of SGC-7901 cell growth between octretide (500ug/L)and 5-FU(50mg/L)(P>0.05).At 48 hours after treatment with octretide(1 mg/L),the morphological changes of apoptosis were seen under fluorescent microscope.At 48 hours after treatment with octretide (500ug/L),most cells were blocked at G_0/G_1 phase(72.07±2.40).The percentage of cells at S phase was decreased signiflcantly(14.99±1.42).The proliferation of cells was inhibited and the apoptosis rate was increased(21.40±2.71).With octretide treatment at different concentrations.IGF-1 level in cell culture fluid was significantly lower than that in the control group(P<0.01),indicating that octretide down-regulated IGF-1 level in the call culture system.Conclusion:Octroetide can inhibit the growth of gastric carcinoma cells in vitro,with no significant inhibition on the growth of non-target cells.Octroetide can induce gastric cancer cell stagnation at G_0/G_1 phase and apoptosis,inhibiting the proliferation directly.Octroetide can also inhibit the secretion of IGF and restrain tumor cell growth indirectly.