Department of General Surgery, Kunhua Hospital Affiliated to Kunming Medical College, Kunming, Yunnan 650032, PR China.
Mol Med Rep. 2012 Sep;6(3):607-10. doi: 10.3892/mmr.2012.966. Epub 2012 Jun 25.
Aquaporin (AQP) water channels are expressed in high-grade tumor cells of different tissue origins. In this study, we investigated whether AQP3 is expressed in cultured MPC-83 pancreatic cancer cells, whether AQP3 enhances cell migration and the signal pathway mechanism involved. MPC-83 pancreatic cancer cells were pre-treated and treated with EGF at different time points and then analyzed using western blotting. Results showed that epidermal growth factor (EGF) induced the phosphorylation of the EGF receptor (EGFR) and extracellular signal-regulated kinase (ERK), which peaked at 5 min after EGF treatment. EGFR and ERK phosphorylation induced by EGF were inhibited by PD153035 (EGFR tyrosine kinase inhibitor) and U0126 (ERK inhibitor), respectively. EGF increased the activity of AQP3 in a dose- and time-dependent manner in MPC-83 pancreatic cancer cells, which peaked at 24 h after treatment. The activity of AQP3 and cell migration were inhibited by PD153035, U0126 and CuSO4 (AQP3 water transport inhibitor). EGFR/ERK pathway-mediated AQP3 activation and cell migration were stimulated by EGF in cultured MPC-83 pancreatic cancer cells in vitro and this cell signaling pathway is inhibited by the EGFR and ERK inhibitors, which may be used as potential therapeutic targets in the treatment of pancreatic cancer.
水通道蛋白（AQP）在不同组织来源的高级别肿瘤细胞中表达。在这项研究中，我们研究了 AQP3 是否在培养的 MPC-83 胰腺癌细胞中表达，以及 AQP3 是否增强细胞迁移以及涉及的信号通路机制。用表皮生长因子（EGF）预处理和处理 MPC-83 胰腺癌细胞，然后在不同时间点使用 Western blot 进行分析。结果表明，表皮生长因子（EGF）诱导 EGF 受体（EGFR）和细胞外信号调节激酶（ERK）的磷酸化，在 EGF 处理后 5 分钟达到峰值。PD153035（EGFR 酪氨酸激酶抑制剂）和 U0126（ERK 抑制剂）分别抑制 EGF 诱导的 EGFR 和 ERK 磷酸化。EGF 以剂量和时间依赖的方式增加 MPC-83 胰腺癌细胞中 AQP3 的活性，在处理 24 小时后达到峰值。PD153035、U0126 和 CuSO4（AQP3 水转运抑制剂）抑制 AQP3 活性和细胞迁移。EGFR/ERK 通路介导的 AQP3 激活和细胞迁移在体外培养的 MPC-83 胰腺癌细胞中受到 EGF 的刺激，该细胞信号通路被 EGFR 和 ERK 抑制剂抑制，这可能成为治疗胰腺癌的潜在治疗靶点。
