Ad-VT oncolytic adenovirus suppresses bladder cancer via cAMP-dependent AMPK-Raptor activation and G2/M arrest
- Tumour Virus Res. 2026 Jan 29:21:200337. doi: 10.1016/j.tvr.2026.200337.
- 1. Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130012, China; Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
- 2. Animal Disease Prevention and Control Center of Helong City, Yanbian Korean Autonomous Prefecture, 130000, China.
- 3. Medical College, Yan Bian University, Yanji, 130000, China.
- 4. Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130012, China.
- 5. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China.
- 6. Department of Neurosurgery, The First Hospital of Jilin University, Changchun, 130012, China. Electronic address: [email protected].
- 7. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China. Electronic address: [email protected].
- 8. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, 130122, China. Electronic address: [email protected].
Bladder Cancer remains a leading cause of cancer-related mortality with limited therapeutic options. This study investigates the antitumor efficacy and mechanism of Ad-VT, a dual-specific oncolytic adenovirus expressing apoptin under the hTERT promoter, in bladder Cancer. In vitro, Ad-VT selectively killed bladder Cancer cells (UM-UC-3, T24, 5637, RT4) while sparing normal urothelial cells (SV-HUC-1), showing dose-dependent cytotoxicity (70 % inhibition at 100 MOI in 5637 cells). It induced G2/M phase arrest via downregulation of cyclin B1/cdc2 and upregulation of p-cdc2/p21. Mechanistically, Ad-VT elevated cAMP levels, activating the AMPK-Raptor-mTOR pathway. This was confirmed by pathway inhibitors (Dorsomorphin, ESI-09) and siRNA knockdown, which reversed cell cycle arrest and reduced cytotoxicity. In vivo, intratumoral Ad-VT injection suppressed UM-UC-3 xenograft growth, enhanced survival, and increased Apoptosis while reducing proliferation. Crucially, AMPK inhibition attenuated Ad-VT's antitumor effects. These results demonstrate that Ad-VT exerts potent, tumor-selective activity against bladder Cancer by inducing cAMP-dependent AMPK-Raptor-mTOR signaling and G2/M arrest, supporting its therapeutic potential.