下调CD44基因表达对人胃癌SGC7901细胞裸鼠移植瘤的抑制作用及其机制

摘要

目的 探讨靶向CD44的短发夹RNA(shRNA)对人胃癌裸鼠移植瘤生长抑制作用及其机制.方法 利用CD44 shRNA细胞及对照细胞株建立裸鼠原位移植瘤及皮下种植瘤模型,监测肿瘤生长变化,采用RT-PCR及免疫组织化学方法检测瘤体内CD44表达的变化,并进一步检测上皮-间质转化(EMT)相关因子表达的变化.结果 成功构建了CD44 shRNA转染荷瘤皮下及原位裸鼠模型.与对照shRNA组、空白对照组分别比较,CD44 shRNA组荷瘤裸鼠肿瘤生长速度减慢,皮下种植瘤及原位移植瘤质量减轻,差异均有统计学意义(P均<0.01).RT-PCR结果发现,CD44 shRNA组CD44 mRNA表达在皮下种植瘤及原位移植瘤均显著下调,差异均有统计学意义(P均<0.01).CD44 shRNA组细胞EMT相关基因E-cadherin表达增加,N-cadherin、Vimentin表达降低.结论 CD44 shRNA可以有效抑制人胃癌SGC7901细胞裸鼠移植瘤生长,并下调CD44的表达水平,这可能与CD44基因参与EMT相关.%Objective This paper studies the inhibitory effect of short hairpin RNA (shRNA) targeting CD44 on the growth of human gastric cancer xenografts in nude mice and its mechanism.Methods The subcutaneous gastric cancer and orthotopic implantation tumor models of nude mice were constructed using CD44 shRNA cells and control cells and tumor growth was observed.Besides, the expression of CD44 was detected using RT-PCR and immunohistochemistry assay.Moreover, the expression of EMT-related factors were further detected.Results The models of nude mice subcutaneous implantation tumor and orthotopic implantation gastric cancer were successfully constructed.Compared with the control shRNA group and the control groups, the tumor in the CD44 shRNA group grew more slowly, and the weight of the subcutaneous tumor and the orthotopic implantation tumor was reduced.The difference was statistically significant(P<0.01).CD44 silencing reduced CD44 mRNA expression in subcutaneous implantation tumor and orthotopic implantation gastric cancer models.The difference was statistically significant(P<0.01).Furthermore, the expression level of EMT-related factors, E-cadherin was increased, while the expression of N-cadherin and Vimentin was reduced.Conclusion CD44 shRNA can effectively inhibit the growth of SGC7901 cells of human gastric cancer xenografts in nude mice, and reduce the expression level of CD44, which may be associated with the EMT procession.