目的：探讨靶向B7H3基因沉默对人恶性血液病细胞株在裸鼠体内成瘤和转移的影响及机制。方法： 应用实时荧光定量PCR（real-time quantitative polymerase chain reaction，qPCR）和流式细胞术（flow cytometry，FCM）检测13株恶性血液病细胞中B7H3分子的表达水平，筛选高表达的U937、Maver和Z138细胞。分别利用慢病毒转染技术靶向敲减B7-H3，建立稳定低表达细胞株，应用qPCR和FCM验证基因沉默效果。将U937、Maver和Z138各自分为空白对照组（non-infected control group，CON）、靶向B7-H3敲减组（B7-H3 knockdown group，KD）和阴性无关序列对照组（negative nontargeted control infected group，NC），将以上9组分别构建裸鼠皮下移植瘤模型，比较肿瘤生长和转移情况，免疫组织化学（immunohistochemistry，IHC）染色检测Ki-67表达，蛋白质免疫印迹法（Western blot）检测基质金属蛋白酶2（matrix metalloproteinase 2，MMP-2）水平。结果： 筛选B7-H3分子高表达的U937、Maver和Z138细胞进行靶向敲减B7-H3，成功建立稳定低表达细胞株。U937、Maver和Z138细胞各自的KD组与NC组比较，观察终点的平均肿瘤生长抑制率分别为61.83%（F=43.78，P<0.05）、59.12%（F=36.51，P<0.05）和67.37%（F=40.29，P<0.05），而各自NC组与CON组相比，肿瘤体积增长趋势差异无统计学意义（P>0.05）。在所有移植瘤裸鼠模型中肝转移最常见，KD组裸鼠的远处转移较相应NC组明显降低。3种细胞各自KD组的Ki-67指数均较相应NC组显著下降(U937移植瘤：40.3%±5.2% vs. 79.1%±6.3%, q=30.31，P<0.05；Maver移植瘤：35.2%±6.4% vs. 69.6%±5.1%, q=24.82，P<0.05；Z138移植瘤：38.4%±7.1% vs. 75.7%±4.8%, q=28.07，P<0.05）， 而NC组与CON组Ki67表达差异无统计学意义（P>0.05）。3种细胞各自KD组肿瘤组织的MMP-2蛋白表达显著降低（U937移植瘤：q=14.59，P<0.05；Maver移植瘤：q=9.25，P<0.05；Z138移植瘤：q=11.04，P<0.05）， NC组与CON组MMP-2表达差异无统计学意义（P>0.05）。结论： 靶向B7-H3基因沉默能够抑制人恶性血液病细胞在裸鼠体内的成瘤和转移能力，其机制可能与Ki-67和MMP-2的表达下调有关。

Objective：To investigate the effect and mechanism of targeted B7-H3 gene silencing on the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. Methods: Real-time fluorogentic quantitative PCR (qPCR) and flow cytometry (FCM) were used to detect the expression of B7-H3 in 13 strains of malignant hematologic cells. Then, U937, Maver and Z138 cells which expressed high level of B7-H3 were screened out. Targeted B7H3 knockdown in U937, Ma-ver and Z138 was performed by lentivirus transduction and the effect of B7-H3 silencing in stable cell lines was tested by qPCR and FCM. Injecting the nine groups subcutaneously into the nude mice to establish xenograft models after dividing the U937, Maver and Z138 into non-infected control group (CON), B7-H3 knockdown group (KD) and negative non-targeted control infected group (NC),respectively, for detecting the tumorigenicity and metastasis in vivo. Furthermore, the expression of Ki-67 in xenograft tumors was detected by immunohistochemistry (IHC). The expression of metalloproteinase 2 (MMP-2) was detected by western blot.  Results: The stable B7-H3 silencing cell lines of U937, Maver and Z138 were successfully established. Compared with the NC group, the KD groups of U937, Maver and Z138 had an obviously slower tumor growth. The average tumor inhibition rates at the end of observation period were 61.83% (F=43.78, P<0.05), 59.12% (F=36.51, P<0.05) and 67.37% (F=40.29, P<0.05); there was no significant difference in tumor volume growth between the NC group and the CON group (P>0.05). The liver distant metastasis of all the xenograft tumor models in nude mice was the most common and the rates of distant metastasis in KD groups were significantly lower than that of the corresponding NC groups. The Ki-67 indexes of the KD groups were significantly lower than those of the relative NC groups in three cell lines (U937: 40.3%±5.2% vs. 79.1%±6.3%, q=30.31, P<0.05, Maver: 35.2%±6.4% vs. 69.6%±5.1%， q=24.82, P<0.05; Z138: 38.4%±7.1% vs. 75.7%±4.8%, q=28.07, P<0.05); there was no significant difference in the expression of Ki-67 between the NC group and the CON group (P>0.05). The expressions of MMP-2 were also significantly lower in the KD groups than in the NC groups (U937: q=14.59, P<0.05; Maver: q=9.25, P<0.05; Z138: q=11.04, P<0.05); there was no significant difference in the expression of MMP-2 between the NC group and the CON group (P>0.05).Conclusion: Targeted B7-H3 gene silencing could inhibit the tumorigenesis and metastasis of human hematological malignancy xenograft tumor in nude mice. The mechanism may be related to the down-regulation of Ki-67 and MMP2.