Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells.
Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells.
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发表时间：
1997-05
期刊：
影响因子：
11.2
通讯作者：
D. He;Z. Mu;X. Le;J. Hsieh;R. Pong;L. Chung;K. Chang
中科院分区：
文献类型：
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作者：
D. He;Z. Mu;X. Le;J. Hsieh;R. Pong;L. Chung;K. Chang
我们以前的研究表明，早幼粒细胞白血病基因PML编码一种生长和转化抑制因子。PML的过表达在体内外均能抑制癌细胞的生长。在这项研究中，我们进一步探索了PML作为一种潜在的药物应用于使用腺病毒递送系统进行前列腺癌基因治疗的可能性。我们构建并生产了由巨细胞病毒强启动子驱动的全长PML重组腺病毒Ad-PML。在LNCaP、DU145和PC-3前列腺癌细胞系中，当感染浓度分别为2、10和100倍(MOI)时，感染效率可达到90%。Western blotting和免疫荧光染色显示AD-PML感染细胞表达高水平的PML蛋白。病毒感染后第3~4天PML蛋白表达达到高峰，第18天可检测到PML蛋白表达。用10MOI和2MOI的Ad-PML感染DU145和LNCaP细胞，观察Ad-PML对前列腺癌DU145和LNCaP细胞生长的影响。我们发现，Ad-PML感染的DU145和LNCaP细胞的生长速度明显受到抑制。裸鼠致瘤性实验表明，经Ad-PML处理的DU145细胞未能形成肿瘤。最重要的是，将Ad-PML直接注射到DU145诱发的肿瘤中，能够抑制裸鼠移植瘤的生长，抑制作用达%。综上所述，这些数据表明PML是前列腺癌的一种肿瘤生长抑制因子，而Ad-PML可能是人类前列腺癌治疗的潜在候选者。
Our previous studies demonstrated that the promyelocytic leukemia gene, PML, encodes a growth and transformation suppressor. Overexpression of PML inhibits cancer cell growth in vitro and in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-adenovirus, Ad-PML, in which the full-length PML cDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 100 multiplicity of infection (MOI), respectively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3-4 postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MOI of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were significantly inhibited. A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad-PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may be a potential candidate for human prostate cancer therapy.