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目的：探讨GHSR1a shRNA慢病毒载体的构建及其对体内直肠癌生长和凋亡的影响。方法构建特异性靶向GHSR1a基因的shRNA慢病毒表达载体和阴性对照序列慢病毒载体；通过慢病毒感染建立稳定表达GHSR1a shRNA的SW480细胞(KD)、阴性对照细胞(NC)及空白对照细胞(BC)，RT-PCR检测GHSR1a mRNA在细胞中的表达；建立裸鼠直肠癌SW480细胞皮下移植瘤模型，实验结束后处死裸鼠并测量各组裸鼠肿瘤重量；免疫组织化学法检测肿瘤组织中Ki-67的阳性表达，TUNEL法检测细胞凋亡。结果在体外实验中，通过荧光表达情况及流式细胞学结果表明成功建立稳定表达GHSR1a shRNA的SW480细胞；SW480细胞感染GHSR1a shRNA后，KD组细胞中GHSR1a mRNA的表达明显高于BC组或NC组(<0.001)；在体内实验中，KD组裸鼠直肠癌皮下移植瘤重量明显低于BC组或NC组(=0.011)；KD组移植瘤细胞凋亡指数明显高于BC组或NC组(<0.001)，同时Ki-67在KD组移植瘤细胞中的阳性表达显著低于BC组或NC组(<0.001)。结论成功建立稳定感染GHSR1a shRNA的直肠癌SW480细胞，沉默GHSR1a后对体内人直肠癌细胞生长有明显抑制作用，并促进细胞凋亡，表明GHSR1a基因有可能成为新的直肠癌治疗作用靶点。“,”Objective To investigate the therapeutic effects of lentivirus-mediated shRNA targeting of Growth Hormone Secretagogue Receptor 1a (GHSR1a) in rectal cancer cell line SW480 in vivo. Methods Human GHSR1a sequence was used for the design of shRNA targeting GHSR1a, which was then introduced to lentivirus, followed by transfection into SW480 cells. Real time quantitative PCR (RT-PCR) was performed to detect the mRNA expression of GHSR1a in rectal cancer cells. In vivo studies, the stable silencing GHSR1a in SW480 xenografts in nude mice were established. After the mice were sacrificed and weighted, immunohistochemistry (IHC) was used to detect the positive expression of Ki-67 in the tumors. TUNEL test kit was used to explore cellular apoptosis in the tumor tissues. Results In vitro study, the tumor-specic lentivirus mediated shRNA targeting GHSR1a gene and GHSR1a knockdown SW480 cells were successfully constructed by fluorescence and flow-cytometry. After transfection with GHSR1a shRNA, the mRNA level of GHSR1a was markedly inhibited in SW480 cells compared with the blank control (BC) or negative control (NC), the difference was statistically significant ( < 0.001). In vivo results demonstrated that down-regulation of GHSR1a in SW480 cells significantly decreased the expression of Ki-67 in tumor tissues ( <0.001), leading to a marked reduction in tumor weight in comparison to BC or NC tumors (=0.011). In addition, apoptosis occurred more frequently in the GHSR1a shRNA transfection group than in control groups ( <0.001). Conclusion Down-regulation of GHSR1a by shRNA technology can effectively inhibit proliferation and promote apoptosis of SW480 cells in vivo, silencing GHSR1a expression could become a novel therapeutic strategy for rectal adenocarcinoma prevention and treatment in the future.