| Autor: |
Ye X; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Ruan JW; Department of Orthopedics, Taizhou Municipal Hospital, Taizhou, China., Huang H; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Huang WP; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China., Zhang Y; Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China., Zhang F; Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. |
| Abstrakt: |
Sustained activation of PI3K-Akt-mTOR cascade is important for renal cell carcinoma (RCC) cell progression. GNE-477 is a novel and efficacious PI3K-mTOR dual inhibitor. The current study tested its anti-RCC cell activity. In the primary cultured human RCC cells, GNE-477 potently inhibited cell growth, viability and proliferation, as well as cell cycle progression, migration and invasion. Furthermore, it induced robust apoptosis activation in primary RCC cells, but being non-cytotoxic to HK-2 epithelial cells and primary human renal epithelial cells. In the primary RCC cells GNE-477 inactivated PI3K-Akt-mTOR cascade by blocking phosphorylation of p85, Akt1, p70S6K1 and S6. Restoring Akt-mTOR activation by a constitutively-active Akt1 reversed GNE-477-induced anti-RCC cell activity. In nude mice intraperitoneal injection of GNE-477 potently suppressed RCC xenograft tumor growth. Collectively, targeting PI3K-Akt-mTOR cascade by GNE-477 inhibits RCC cell growth in vitro and in vivo . |
