School of Pharmacy, Bengbu Medical College, Anhui, Bengbu, 233030, PR China.
College of Life Sciences, Nanjing University, Jiangsu, Nanjing, 210093, PR China.
Biomed Pharmacother. 2019 Sep;117:109090. doi: 10.1016/j.biopha.2019.109090. Epub 2019 Jun 12.
Pannexin (Panx) plays a crucial role in several cellular processes such as immune cell death, cell proliferation, invasion, and migration, apoptosis, and autophagy. However, the role of Panx in regulating cell migration and invasion in testicular cancer remains to be elucidated. In the present study, we determined the correlation between Panx-1 channel function and migration and invasion in I-10 testicular cancer cells. Transwell and wound healing assays showed that inhibition of Panx-1 by carbenoxolone (CBX) and probenecid (PBN) attenuated the migration and invasion of testicular cancer cells in vitro. Moreover, knockdown of Panx-1 with short hairpin RNA (shRNA) remarkably decreased the migration and invasion ability of I-10 cells. In shRNA-transfected cells, extracellular ATP (released through Panx channel) was also found to be decreased. Similarly, overexpression of Panx-1 with mPanx-1 increased the migration and invasion ability of I-10 cells. Moreover, we found that in mPanx-1-transfected cells treated with U0126 (inhibitor of p-ERK1/2), the migration and invasion of I-10 cells were remarkably attenuated. Overall, increased Panx-1 promotes migration and invasion in testicular cancer cells, and the effect is probably be related with ERK1/2 kinase activity. Thus, Panx-1 can serve as a potential therapeutic target for the treatment of testicular cancer.
质膜通道蛋白（Panx）在多种细胞过程中发挥着关键作用，如免疫细胞死亡、细胞增殖、侵袭和迁移、细胞凋亡和自噬。然而，Panx 在调节睾丸癌中细胞迁移和侵袭中的作用仍有待阐明。在本研究中，我们确定了 Panx-1 通道功能与 I-10 睾丸癌细胞迁移和侵袭之间的相关性。Transwell 和划痕愈合实验表明，Carbenoxolone (CBX) 和 Probenecid (PBN) 抑制 Panx-1 可减弱体外睾丸癌细胞的迁移和侵袭。此外，短发夹 RNA (shRNA) 敲低 Panx-1 可显著降低 I-10 细胞的迁移和侵袭能力。在 shRNA 转染的细胞中，也发现细胞外 ATP（通过 Panx 通道释放）减少。同样，mPanx-1 的过表达增加了 I-10 细胞的迁移和侵袭能力。此外，我们发现 mPanx-1 转染的细胞在用 U0126（p-ERK1/2 抑制剂）处理后，I-10 细胞的迁移和侵袭明显减弱。总之，Panx-1 的增加促进了睾丸癌细胞的迁移和侵袭，其作用可能与 ERK1/2 激酶活性有关。因此，Panx-1 可以作为治疗睾丸癌的潜在治疗靶点。
