生长抑素作用Cmet抑制肝细胞癌生长的研究

目的　观察生长抑素 (Somatostatin ,SST)对Bel74 0 2肝癌细胞株以及裸鼠种植瘤生长的影响 ,同时探索SST的抑瘤机制。方法　以裸鼠人肝癌转移模型为材料 ,观察SST对种植瘤生长的影响。以MTT法测量SST对Bel74 0 2细胞增殖的影响 ,光镜下观察细胞形态的变化。以细胞迁移实验和粘附实验观察细胞侵袭和粘附能力的影响。以流式细胞仪测量细胞周期及细胞表面肝细胞生长因子受体Cmet表达的影响 ,以及检测细胞表面生长抑素受体 2 (somatostatinreceptor 2 ,SSTR2 )的阳性率。 结果　SST治疗可以明显抑制裸鼠人肝癌种植瘤的生长 ,但SST处理的 74 0 2细胞增殖能力和细胞形态无明显改变 ,细胞的侵袭和粘附能力可见明显下降 ,细胞生长静止期 (G0 /G1)的比例显著增加 (0 .4 80± 0 .0 32vs 0 .5 77± 0 .0 0 9) ,但未见凋亡峰 ,细胞表面可见SSTR2的表达 ,SST可使细胞Cmet的表达明显受抑。结论　SST能通过与SSTR结合抑制肝癌的生长 ,减少Cmet的表达可能是抑瘤的一个重要机制 ,而并非直接杀死肝癌细胞和诱导凋亡。

Inhibition effects of Somatostatin on hepatocellular carcinoma in vitro and in vivo

Objective:To observe the effects of Somatostatin on the proliferation,invasion and adhesion of Bel7402 hepatocellular carcinoma(HCC) cell line and on the growth of HCC xenografts in nude mice.Methods:Nude mice bearing xenografts of cell line were treated with Somatostatin or saline control for 7 weeks after tumor implantation. The effect of Somatostatin on proliferative ability of Bel7402 cells was observed by MTT chromometry.The cell morphologic change was observed by light microscope, the adhesive and invasive ability of 7402 cells by cell adhesion and migration experiments, the Cmet (hepatocyte growth factor repceptor) expression, the cell cycle of 7402 cells and the expression of SSTR2 (somatostatin receptor 2) in 7402 cells by immunofluorescence flow cytometry.Results:The mean tumor weight in mice given Somatostatin was significantly lower than that of the control group. After the treatment with Somatostatin, the proliferative ability and cell form of 7402 cells didn't change significantly, the adhesive and invasive ability decreased significantly; the ratio of cells in resting state (G0/G1) increased, but no apoptosis peak was observed. The Cmet expression in 7402 cells decreased significantly and SSTR2 was detected in 44.3% of 7402 cells.Conclusions: Somatostatin could inhibit the growth of HCC by combining with SSTR. It may be an important mechanism for Somatostatin to inhibit tumor by decreasing the Cmet expression in HCC cells, rather than by killing the liver cancer cells or inducing apoptosis directly.