Hum Gene Ther 2011 Oct;22 (10): 1201-8. [IF:4.829]
Lentivirus-mediated RNA interference targeting bax inhibitor-1 suppresses ex vivo cell proliferation and in vivo tumor growth of nasopharyngeal carcinoma.
Li XY , Lai YK , Zhang JF , Luo HQ , Zhang MH , Zhou KY , Kung HF .
1 Institute of Biochemistry and Molecular Biology , Guangdong Medical College, Zhanjiang, Guangdong 524023, China .
广东医学院生物化学与分子生物学研究所
Abstract
Abstract Bax inhibitor-1 (Bi-1), an anti-apoptotic protein that belongs to the Bcl-2 family, plays an important role in the mitochondrial apoptosis pathway to suppress Bax-induced apoptosis. In several human cancers, including nasopharyngeal carcinoma, its expression was found to be increased; however, up-regulated expression of this protein has been linked to increased cell proliferations. In this study, we down-regulated the gene expression of Bi-1 in nasopharyngeal carcinoma cells by using a lentivirus transfection system packed with short hairpin RNA targeting Bi-1 and used an in vivo model to assess its efficacy as a target in human gene therapy. The data indicated that human malignant nasopharyngeal carcinoma cells, CNE-1 and SUNE-1, transfected with lentiviral short hairpin RNA targeting Bi-1 grew more slowly and showed a higher degree of apoptosis. Moreover, the tumorigenicity of CNE-1 was significantly suppressed when inoculated mice were intratumorically injected with the same vector. Taken together, these data lead us to conclude that Bi-1 plays a crucial role in CNE-1 tumorigenesis and that Bi-1 may be a novel therapeutic target for nasopharyngeal carcinoma.
摘要：
Bax-1抑制剂（Bi-1）是Bcl-2家族的一种抗凋亡蛋白，在抑制由Bax诱导的线粒体凋亡通路中发挥重要作用。在多种人类癌症（包括鼻咽癌）中，均发现Bi-1蛋白的增加。该蛋白表达的上调与细胞增殖相关。在本研究中，我们用包含靶向Bi-1的sh-RNA慢病毒转移载体下调鼻咽癌细胞中Bi-1基因的表达。同时我们在体内动物模型中评价该基因治疗药物的有效性。数据显示，转移了包含靶向Bi-1的sh-RNA慢病毒转移载体的人类转移性鼻咽癌肿瘤细胞株CNE-1和SUNE-1生长速度变慢，凋亡增加。而且，在瘤内注射这个载体后，接种在小鼠体内的CNE-1细胞株的致瘤性受到显著抑制。综上所述，通过这些数据，我们得到结果，Bi-1在CNE-1的致瘤性中发挥重要作用。Bi-1可能是鼻咽癌的一个新的治疗靶标。
