NDV-D90 suppresses growth of gastric cancer and cancer-related vascularization

Abstract

// Hong Sui 1, * , Kaibing Wang 2, * , Rui Xie 1, * , Xi Li 3 , Kunpeng Li 3 , Yuxian Bai 1 , Xishan Wang 4 , Bin Bai 2 , Dan Chen 1 , Jiazhuang Li 1 , Baozhong Shen 5 1 Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, China 2 Department of Intervention, The Second Hospital Affiliated Harbin Medical University, Harbin 150086, China 3 Division of Swine Disease, National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Medicine, Harbin 150069, China 4 Department of Abdominal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China 5 Department of Radiology, The Fourth Hospital of Harbin Medical University, Harbin 150001, China * These authors contributed equally to this work and are joint First authors Correspondence to: Baozhong Shen, email: shenbaozhong2016@163.com Hong Sui, email: suihong2003@yeah.net Keywords: gastric cancer, newcastle disease viruses (NDV), apoptosis, vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) Received: March 01, 2017      Accepted: March 15, 2017      Published: March 25, 2017 ABSTRACT Recent reports suggest promises on using oncolytic Newcastle disease viruses (NDV) to treat different cancers, while the effects of a NDV-D90 strain on gastric cancer remain unknown. Here we showed that NDV-D90 induced gastric cancer cell apoptosis in a dose-dependent manner in 3 gastric cancer cell lines BGC-823, SGC-7901 and MKN-28. Pronounced reduction in cell invasion was detected in NDV-D90-treated BGC-823 and SGC-7901 cells, but not in MKN-28 cells. The increases in cell apoptosis and reduction in cell growth in NDV-D90-treated gastric cancer cells seemingly resulted from augmentation of p38 signaling and suppression of ERK1/2 and Akt signaling. In vivo , orthotopic injection of NDV-D90 impaired tumor growth and induced intratumoral necrosis. Tumor cells that had been pre-treated with NDV-D90 showed defect in development of implanted tumor. Moreover, NDV-D90 appeared to reduce gastric tumor vascularization, possibly through suppression of vascular endothelial growth factor A and Matrix Metallopeptidase 2. Together, our data suggest that NDV-D90 may have potential anti-cancer effects on gastric cancer.