Adenovirus-mediated PEDF expression inhibits prostate cancer cell growth and results in augmented expression of PAI-2
Adenovirus-mediated PEDF expression inhibits prostate cancer cell growth and results in augmented expression of PAI-2
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DOI：
10.4161/cbt.6.3.3757
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Lu, Yuan
中科院分区：
文献类型：
--
作者：
Guan, Ming;Jiang, Haowen;Lu, Yuan
PEDF是最有效的血管生成抑制剂之一。PEDF的缺失在人前列腺肿瘤中发现，并与向转移表型的进展相关。为了检测PEDF的治疗潜力，我们构建了一种能够在PC-3前列腺癌细胞中有效转导和表达PEDF的复制缺陷型腺病毒载体（Ad-PEDF）。作为对照，我们使用腺病毒表达β-半乳糖苷酶（Ad-LacZ）。我们发现，PEDF的过表达抑制细胞的增殖和增加血清饥饿的细胞凋亡，与Ad-LacZ相比。此外，Ad-PEDF抑制软琼脂中的锚定非依赖性生长细胞和与微血管密度降低相关的无胸腺裸鼠肿瘤形成。基因芯片分析结果显示，在8464个基因中，有56个基因在感染Ad-PEDF的PC-3细胞中表达上调或下调。差异表达基因涵盖了广泛的功能活性，包括催化活性，蛋白结合，信号转导活性和细胞侵袭。其中，派-2和DRHC被证实上调与实时PCR和蛋白质印迹，提示可能与PEDF诱导的细胞运动和转移信号。这些结果有助于我们理解PEDF治疗前列腺癌的分子机制。
PEDF is one of the most potent inhibitor of angiogenesis. Loss of PEDF was found in human prostate tumors and associated with the progression toward a metastatic phenotype. To test the therapeutic potential of PEDF, we constructed a replication-defective adenoviral vector capable of efficient transduction and expression of PEDF (Ad-PEDF) in PC-3 prostate carcinoma cells. As controls, we used adenoviruses expressing b-galacto sidase (Ad-LacZ). We showed that overexpression of PEDF inhibited proliferation of cells and augmented apoptosis in serum-starved cells, in comparison with Ad-LacZ. Furthermore, Ad-PEDF suppresses anchorage-independent growth cells in soft agar and tumor formation in athymic nude mice associated with decreased microvessel density. Microarray analysis showed that 56 out of 8464 genes were found to be upregulated and downregulated in the PC-3 infected with Ad-PEDF as compared with Ad-LacZ. The differentially expressed genes cover a broad range of functional activities including catalytic activity, protein binding, signal transduction activity and cell invasion. Among them, PAI-2 and DRHC were confirmed to be upregulated with real-time PCR and Western blot, suggesting a possible association with PEDF-induced signaling for cell motility and metastasis. These results can contribute to our understanding of the molecular mechanisms of treatment strategies of PEDF for prostate cancer.