奥曲肽抑制胃癌侵袭和转移的实验研究

目的　通过体外及体内实验 ,研究生长抑素类似物奥曲肽对胃癌侵袭和转移的影响 ,并初步探讨其作用机制。方法　选用改良的BoydenChamber膜侵袭系统 ,观察奥曲肽对胃癌细胞迁移和侵袭的影响 ;建立裸鼠人胃癌原位移植瘤模型 ,给予奥曲肽皮下注射治疗 8周后 ,观察胃癌转移情况 ;免疫细胞化学染色检测奥曲肽对胃癌细胞血管内皮生长因子 (VEGF)表达的影响 ;用明胶酶法及RT PCR法了解奥曲肽是否下调胃癌细胞MMP 2表达及MMP 2mRNA的表达。结果　经奥曲肽作用后 ,体外培养的胃癌细胞的趋化细胞数 (5 0± 4 )或侵袭细胞数 (30± 3)均明显低于对照组 (10 7± 11,5 6± 5 ,均P <0 0 1)。奥曲肽明显降低裸鼠人胃癌移植瘤的转移 ,其肿瘤血管的形成数亦明显低于对照组。此外 ,奥曲肽降低胃癌细胞VEGF的表达 ,明显下调MMP 2mRNA的表达 ,导致MMP 2的合成减少。结论　奥曲肽能有效抑制胃癌侵袭和转移。其作用机制可能与降低胃癌细胞运动能力、抑制MMP 2表达及肿瘤血管形成有关

Inhibition of human gastric cancer metastasis by ocreotide in vitro and in vivo

OBJECTIVE: To study the effect of somatostatin analogue octreotide on the invasion and metastasis of gastric cancer in vitro and in vivo. METHODS: A nude mouse model of transplanted in situ human gastric cancer was established by implanting SGC-7901 human gastric cancer cells under the skin of nude rats. Twelve experimental animals were divided into two groups, 6 in each group: octreotide group and control group subcutaneously injected with octreotide of the dose of 100 microgram /g(-1) / (-1) and normal saline of the same dose respectively for 8 weeks. By the end of the 8(th) week, the animals were killed and the tumors were taken out to be examined pathologically. Metastasis was observed too. Microvascular density and VEGF expression were examined by immunohistochemistry with factor VIII and VEGF antibody. The expression of MMP-2 gene in gastric cancer cell was examined by gelatin zymography and RT-PCR. The upper chamber cavity walls of membrane invasion culture system were covered with matrigel and SGC-7901 cells and octreotide were added into the chambers. After 12 hours' culture, the migration and invasion of cancer cells were observed. RESULTS: In the membrane invasion culture system, the numbers of invading and migrating SGC-7901 cells were significantly lower in octreotide group than in the control group. Metastasis was seen in 4 of the 6 control mice and was seen in only one of the 6 octreotide treated mice. The microvascular density was lower in octreotide treated mice than in the control. The VEGF and MMP-2 expression was inhibited by octreotide. CONCLUSION: Octreotide inhibits the migration and invasion of SGC-7901 gastric cancer cells in vitro and inhibits the metastasis of cancer in vivo. Tha mechanism may be down-regulation of MMP-2 expression and decrease of tumor angiogenesis.