Chen Chen, Ma Ting, Zhang Chao, Zhang Hao, Bai Lijuan, Kong Lingyi, Luo Jianguang
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
Mol Carcinog. 2017 Dec;56(12):2692-2705. doi: 10.1002/mc.22712. Epub 2017 Sep 11.
Epithelial-mesenchymal transition (EMT) has emerged as an important determinant role in colorectal cancer (CRC) metastasis. It has been reported that aquaporin 5 (AQP5) is closely linked to CRC metastasis. However, the effect of AQP5 on the EMT process of CRC remains unknown. The current study showed that overexpression of AQP5 activated EMT in CRC cells. Cairicoside E (CE), a natural resin glycoside compound isolated from Ipomoea cairica, showed promising cytotoxic activity in our previous report. Further investigation found that CE inhibited the expression of AQP5 and the EMT process. Moreover, the inhibitory effect of CE on EMT was reversed by overexpression of AQP5. Importantly, CE also suppressed the EMT and p-Smad2/3 induced by TGF-β1. On the other hand, overexpression of AQP5 up-regulated the p-Smad2/3, which resulted in the activation of EMT. After silencing of AQP5, CE had no significant effect on EMT markers and p-Smad2/3 induced by TGF-β1, indicating that CE inhibited the EMT through down-regulation of AQP5 and suppression of p-Smad2/3. CE also inhibited the AQP5 expression in the lung metastatic nodules of HCT-116 cells in vivo. Our findings suggested that CE may serve as a promising drug for the treatment of CRC metastasis.
上皮-间质转化（EMT）已成为结直肠癌（CRC）转移的一个重要决定性因素。据报道，水通道蛋白5（AQP5）与CRC转移密切相关。然而，AQP5对CRC上皮-间质转化过程的影响尚不清楚。目前的研究表明，AQP5的过表达激活了CRC细胞中的上皮-间质转化。在我们之前的报告中，从五爪金龙中分离出的天然树脂糖苷化合物凯瑞皂苷E（CE）显示出有前景的细胞毒性活性。进一步研究发现，CE抑制AQP5的表达以及上皮-间质转化过程。此外，AQP5的过表达逆转了CE对上皮-间质转化的抑制作用。重要的是，CE还抑制了TGF-β1诱导的上皮-间质转化和p-Smad2/3。另一方面，AQP5的过表达上调了p-Smad2/3，从而导致上皮-间质转化的激活。沉默AQP5后，CE对TGF-β1诱导的上皮-间质转化标志物和p-Smad2/3没有显著影响，这表明CE通过下调AQP5和抑制p-Smad2/3来抑制上皮-间质转化。CE在体内也抑制了HCT-116细胞肺转移结节中的AQP5表达。我们的研究结果表明，CE可能是一种有前景的治疗CRC转移的药物。
