Cancer Epigenetics Group, Research Center of the Portuguese Oncology Institute, Porto, Portugal.
Epigenetics. 2013 May;8(5):548-58. doi: 10.4161/epi.24519. Epub 2013 Apr 17.
Prostate cancer (PCa) is one of the most incident malignancies worldwide. Although efficient therapy is available for early-stage PCa, treatment of advanced disease is mainly ineffective and remains a clinical challenge. microRNA (miRNA) dysregulation is associated with PCa development and progression. In fact, several studies have reported a widespread downregulation of miRNAs in PCa, which highlights the importance of studying compounds capable of restoring the global miRNA expression. The main aim of this study was to define the usefulness of enoxacin as an anti-tumoral agent in PCa, due to its ability to induce miRNA biogenesis in a TRBP-mediated manner. Using a panel of five PCa cell lines, we observed that all of them were wild type for the TARBP2 gene and expressed TRBP protein. Furthermore, primary prostate carcinomas displayed normal levels of TRBP protein. Remarkably, enoxacin was able to decrease cell viability, induce apoptosis, cause cell cycle arrest, and inhibit the invasiveness of cell lines. Enoxacin was also effective in restoring the global expression of miRNAs. This study is the first to show that PCa cells are highly responsive to the anti-tumoral effects of enoxacin. Therefore, enoxacin constitutes a promising therapeutic agent for PCa.
前列腺癌（PCa）是全球最常见的恶性肿瘤之一。尽管早期 PCa 有有效的治疗方法，但晚期疾病的治疗主要无效，仍然是一个临床挑战。 microRNA（miRNA）失调与 PCa 的发生和发展有关。事实上，有几项研究报告称，miRNA 在 PCa 中广泛下调，这凸显了研究能够恢复全局 miRNA 表达的化合物的重要性。本研究的主要目的是由于依诺沙星能够以 TRBP 介导的方式诱导 miRNA 生物发生，来定义依诺沙星作为 PCa 抗肿瘤剂的有用性。使用一组五种 PCa 细胞系，我们观察到它们全部为 TARBP2 基因的野生型，并表达 TRBP 蛋白。此外，原发性前列腺癌显示出正常水平的 TRBP 蛋白。值得注意的是，依诺沙星能够降低细胞活力，诱导细胞凋亡，引起细胞周期停滞，并抑制细胞系的侵袭性。依诺沙星还能有效恢复 miRNA 的全局表达。这项研究首次表明，PCa 细胞对依诺沙星的抗肿瘤作用高度敏感。因此，依诺沙星构成了治疗 PCa 的一种有前途的治疗剂。
