Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Research Center of Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China.
Cancer Gene Ther. 2012 Oct;19(10):690-6. doi: 10.1038/cgt.2012.52. Epub 2012 Aug 24.
Transcriptional positive coactivator 4 (PC4) is a multifunctional nuclear protein that has important roles in DNA transcription, replication, repair and heterochromatinization. However, the role of PC4 in cancer remains to be clarified. Several studies propose that PC4 may act as a putative tumor suppressor. Here, we demonstrate for the first time that PC4 may represent a potential therapeutic target in non-small cell lung cancer (NSCLC). PC4 protein expression is significantly upregulated in NSCLC carcinoma tissues compared with their adjacent noncancerous counterparts as shown by immunohistochemical staining and western blotting in 104 pairs of formalin-fixed human NSCLC specimens and 6 fresh NSCLC samples. Knockdown of PC4 expression by sequence-specific small interfering RNA (siRNA) in human NSCLC cells (A549, H460 and H358) significantly inhibits the growth of cancer cells by the induction of cell cycle arrest and the increase of cell apoptosis in vitro. Interrupting the PC4 signaling pathway by injection of the PC4 siRNA liposome complex produced an effective regression of pre-established A549 cell xenografts in mice through growth inhibition and increased apoptosis. These results indicated that PC4 could be an attractive new therapeutic target for the treatment of NSCLC.
转录共激活因子 4（PC4）是一种多功能核蛋白，在 DNA 转录、复制、修复和异染色质形成中具有重要作用。然而，PC4 在癌症中的作用仍有待阐明。一些研究表明，PC4 可能作为一种潜在的肿瘤抑制因子发挥作用。在这里，我们首次证明 PC4 可能是非小细胞肺癌（NSCLC）的一个潜在治疗靶点。通过对 104 对福尔马林固定的人 NSCLC 标本和 6 个新鲜 NSCLC 样本进行免疫组织化学染色和 Western blot 分析，发现 PC4 蛋白表达在 NSCLC 癌组织中明显上调，与相邻的非癌组织相比。通过特异性小干扰 RNA（siRNA）敲低人 NSCLC 细胞（A549、H460 和 H358）中的 PC4 表达，可显著抑制体外细胞周期停滞和细胞凋亡的诱导，从而抑制癌细胞的生长。通过注射 PC4 siRNA 脂质体复合物中断 PC4 信号通路，可通过抑制生长和增加凋亡，有效抑制预先建立的 A549 细胞异种移植物在小鼠中的生长。这些结果表明，PC4 可能是治疗 NSCLC 的一个有吸引力的新治疗靶点。
