1. Academic Validation
  2. Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function

Aspirin Inhibits Natural Killer/T-Cell Lymphoma by Modulation of VEGF Expression and Mitochondrial Function

  • Front Oncol. 2019 Jan 14;8:679. doi: 10.3389/fonc.2018.00679.
Hongyu Zhang 1 Jianping Lu 2 Yun Jiao 3 Qi Chen 1 Min Li 4 Zichen Wang 2 Zhendong Yu 1 Xiaodong Huang 4 Athena Yao 4 Qiong Gao 5 Weiguo Xie 4 Ling Li 3 Paul Yao 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, China.
  • 2 Department of Child Psychiatry, Kangning Hospital of Shenzhen, Shenzhen, China.
  • 3 Department of Pediatrics, Hainan Maternal and Child Health Hospital, Haikou, China.
  • 4 Institute of Rehabilitation Center, Tongren Hospital of Wuhan University, Wuhan, China.
  • 5 Department of Gynecology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.
Abstract

Extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) is an Epstein-Barr virus (EBV)-associated lymphoma with a strong tendency relapse or be refractory in response to chemotherapy. Development of a new strategy for NKTCL treatment is still quite necessary. In this study, we found that aspirin treatment suppresses VEGF expression in NKTCL SNK-6 cells. Further investigation showed that aspirin treatment increases histone methylation in the range of -100~0 that is proximal to the transcription start site on the VEGF promoter, subsequently decreasing the binding ability of Sp1 to the VEGF promoter with VEGF suppression. Furthermore, aspirin treatment modulates mitochondrial function with increased ROS formation and Apoptosis in NKTCL cells. Aspirin treatment alone slightly inhibits NKTCL SNK-6 tumor growth and EBV replication; while in the presence of histone deacetylase inhibitor (HDACi) chidamide (CDM), aspirin significantly suppresses the VEGF signaling pathway with increased ROS overgeneration and EBV inhibition. We also showed that with the addition of chidamide, aspirin significantly suppresses NKTCL tumor growth in both in vitro Cell Culture and in vivo mouse model with prolonged mouse survival. This is the first time that the potential mechanism for aspirin-mediated VEGF suppression and anti-tumor effect has been discovered, and this study provides a new strategy for anti-tumor drug development for NKTCL treatment based on aspirin-mediated targeting of the VEGF signaling pathway and ROS formation.

Keywords

NKTCL; aspirin; epstein-barr virus; mitochondria; reactive oxygen species.

Figures
Products