title: BCL-2 inhibition impairs mitochondrial function and targets oral tongue squamous cell carcinoma.
abstract: OBJECTIVE
  To understand the role of Bcl-2 overexpression in oral tongue squamous cell carcinoma (OTSCC) patients and investigate the efficacy of targeting Bcl-2 in OTSCC.
  
  
  METHODS
  The expression level of Bcl-2 on normal tongue cells and OTSCC cells were measured by real-time PCR and western blotting. The functional roles of Bcl-2 were examined by MTS, flow cytometry and xenograft cancer mouse model. Mechanism studies were performed by analyzing mitochondrial functions in a panel of OTSCC cell lines.
  
  
  RESULTS
  Bcl-2 is up-regulated at mRNA and protein levels in a panel of OTSCC cell lines compared to normal tongue epithelial cells (NTEC). Importantly, overexpression of Bcl-2 confers resistance of OTSCC cells to chemotherapeutic drug cisplatin treatment. Overexpression of Bcl-2 in NTEC significantly increased cell growth. In contrast, inhibition of Bcl-2 by genetic and pharmacological approaches inhibits proliferation and induces apoptosis in OTSCC cells. Mechanistically, Bcl-2 inhibitor ABT-199 impairs mitochondrial functions as shown by the decreased levels of mitochondrial membrane potential, mitochondrial respiration and ATP, and the increased levels of ROS in OTSCC cells. In addition, ABT-199 inhibits proliferation and induces apoptosis and mitochondrial dysfunctions in NTEC cells, but to a less extent than in OTSCC cells. We further show that ABT-199 augments the effects of cisplatin in eliminating OTSCC cells in in vitro tongue cancer cellular system and in vivo tongue cancer xenograft mouse model.
  
  
  CONCLUSIONS
  Inhibition of Bcl-2 effectively targets OTSCC cells through inhibiting proliferation and inducing apoptosis. Inhibition of Bcl-2 also augments the inhibitory effects of cisplatin in vitro and in vivo.
authors.affiliation: Department of Oral Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Oral Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Oral Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Oral Medicine, The Second Clinical Medical College, Yangtze University, Jingzhou Central Hospital, Jingzhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Clinical Medicine, Hubei College of Chinese Medicine, Academy Road 87, Jingzhou, 434020 People's Republic of China.
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Wang
keywords: ABT-199; Bcl-2; Mitochondria; Tongue squamous carcinoma