Department of Urology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
Department of Medical Engineering, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan.
Oncol Rep. 2017 Oct;38(4):2197-2204. doi: 10.3892/or.2017.5902. Epub 2017 Aug 11.
Signal transducer and activator of transcription 3 (STAT3) regulates the expression of genes mediating cell survival, proliferation and angiogenesis and is aberrantly activated in various types of malignancies, including bladder cancer. We examined whether it could be a novel therapeutic target for bladder cancer using the STAT3 inhibitor WP1066. In T24 and UMUC-3 bladder cancer cells, 5 µM WP1066 prevented the phosphorylation of STAT3 and 2.5 µM WP1066 decreased cell survival and proliferation significantly (P<0.01). WP1066 also induced apoptosis accompanied by the suppression of the expression of Bcl-2 and Bcl-xL in T24 cells. Moreover, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased significantly (P<0.01) when cells were treated with WP1066. The activities of MMP-2 and MMP-9 were also decreased by treatment with 10 µM WP1066. Our results revealed that using WP1066 to inhibit the STAT3 signaling pathway suppressed the viability and invasiveness of bladder cancer cells effectively and could be a novel therapeutic strategy against bladder cancer.
信号转导子和转录激活子 3（STAT3）调节介导细胞存活、增殖和血管生成的基因表达，并且在包括膀胱癌在内的各种类型的恶性肿瘤中异常激活。我们使用 STAT3 抑制剂 WP1066 研究了它是否可以成为膀胱癌的新治疗靶点。在 T24 和 UMUC-3 膀胱癌细胞中，5 μM WP1066 可阻止 STAT3 的磷酸化，而 2.5 μM WP1066 则显著降低细胞存活率和增殖（P<0.01）。WP1066 还诱导 T24 细胞凋亡，并抑制 Bcl-2 和 Bcl-xL 的表达。此外，当用 WP1066 处理细胞时，通过划痕实验检测到的覆盖面积和穿过 Matrigel 室的细胞数量明显减少（P<0.01）。用 10 μM WP1066 处理还降低了 MMP-2 和 MMP-9 的活性。我们的研究结果表明，使用 WP1066 抑制 STAT3 信号通路可有效抑制膀胱癌细胞的活力和侵袭性，可能成为治疗膀胱癌的新策略。
