Liao Alex Chien Hwa, Kuo Chia-Cheng, Huang Yei-Chung, Yeh Chi-Wei, Hseu You-Cheng, Liu Jer-Yuh, Hsu Li-Sung
Division of Urology, Department of Surgery, Chi‑Mei Foundation Medical Center, Tainan, Taiwan, R.O.C.
Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, R.O.C.
Mol Med Rep. 2014 Sep;10(3):1531-6. doi: 10.3892/mmr.2014.2375. Epub 2014 Jul 14.
Bladder cancer is one of the causes of cancer‑related death and has a high mortality rate due to its metastatic ability. Naringenin, a bioactive compound predominantly found in citrus fruits, exhibits several cellular functions, including anti‑oxidant, ‑lipidemia and ‑cancer abilities. However, the effects of naringenin on bladder cancer cells are yet to be elucidated. The present study investigated the molecular mechanisms underlying the effects of naringenin on the migration of TSGH‑8301 bladder cancer cells. Treatment with naringenin at doses ranging between 0 and 300 µM over a period of 24 h was found to reduce cell viability. Furthermore, zymography and western blot analysis revealed that naringenin reduced the expression of matrix metalloproteinase (MMP)‑2 in a dose‑dependent manner, and repressed its activity. Naringenin also reduced TSGH‑8301 cell migration in a concentration‑dependent manner, as evidenced by wound healing and Transwell® assays. In addition, naringenin was found to inhibit AKT activity and block the nuclear translocation of nuclear factor κ‑light‑chain‑enhancer of activated B cells. In conclusion, the findings of the present study show that naringenin is capable of inhibiting bladder cancer cell migration through the downregulation of the AKT and MMP‑2 pathways.
膀胱癌是癌症相关死亡的原因之一，因其转移能力而具有较高的死亡率。柚皮素是一种主要存在于柑橘类水果中的生物活性化合物，具有多种细胞功能，包括抗氧化、降血脂和抗癌能力。然而，柚皮素对膀胱癌细胞的影响尚待阐明。本研究调查了柚皮素对TSGH-8301膀胱癌细胞迁移影响的分子机制。发现在24小时内用0至300μM剂量的柚皮素处理可降低细胞活力。此外，酶谱分析和蛋白质印迹分析表明，柚皮素以剂量依赖性方式降低基质金属蛋白酶（MMP）-2的表达，并抑制其活性。如伤口愈合和Transwell®分析所示，柚皮素还以浓度依赖性方式减少TSGH-8301细胞迁移。此外，发现柚皮素可抑制AKT活性并阻断活化B细胞核因子κ-轻链增强子的核转位。总之，本研究结果表明，柚皮素能够通过下调AKT和MMP-2途径抑制膀胱癌细胞迁移。
